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Spinal cord injury (SCI) is a relatively common and lethal dangerous disease of the central nervous system, for which there is a lack of effective clinical treatments. It has been found that mesenchymal stem cell-derived exosomes (MSC-Exos) play a key role in alleviating SCI through mechanisms such as regulating the microenvironment, promoting angiogenesis, and facilitating axonal regeneration. However, the drawbacks of natural exosomes, such as low yield, weak activity, and low targeting ability, limit their clinical applications. In recent years, MSCs-Exos have gradually become a research hotspot for treating SCI through miRNA modulation, combined hydrogel, and preculture. In addition, exosomes as good biocompatible drugs, nucleic acid, and other delivery carriers have shown a broad application prospect in treating SCI. This article summarizes the pathogenesis of SCI and the research progress of MSC-Exos in the treatment of SCI in recent years, and provides a systematic review of the mechanisms of MSC exosomes and their combination with different modalities in the treatment of SCI., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The frequency occurrence of building fires necessitates response materials with high flame retardancy and temperature sensitivity. Herein, we synthesized a gelatin/poly(acrylamide-co-acrylic acid)/lithium bromide/sodium phytate/glycerol hydrogel (Gly-GAPL) using in situ radical polymerization and solvent exchange techniques. Gly-GAPL exhibits notable thermoelectric performance (the Seebeck coefficient: 8.66 mV/K), temperature sensitivity, commendable mechanical properties and flame retardancy. Remarkably, Gly-GAPL features a rapid response time, triggering an alarm within 2 s upon exposure to flame. Gly-GAPL is highly resistant to ignition and significantly enhances the fire resistance of wood coated with it. Furthermore, its high transparency, impressive water retention and adhesion further underscore its potential as a flame-retardant coating for various inflammable materials. Given its outstanding thermoelectric performance and temperature sensitivity, an early fire-warning system is rapidly activated, promptly sending alerts to smart devices. This work introduces a novel strategy for developing smart flame retardancy materials and advances the applications of ionic hydrogels in early fire-warning systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2., (© 2024 Chan et al.)

Alkaloids are the main medicinal components in Houttuynia cordata. In this study, two accessions 6# and 7# of H. cordata underwent thorough metabolomic analyses to identify and quantify alkaloid phytometabolites. It turned out that the alkaloid types were largely similar between 6# and 7#, and the identified 81 alkaloids could be divided into nine structural classes. However, the content of alkaloids in the two accessions was quite different. According to transcriptome data, a total of 114 differentially expressed genes related to alkaloid metabolism were screened. The alkaloid synthesis pathway of the two varieties was mainly different in the isoquinoline alkaloid biosynthesis and indole alkaloid biosynthesis; four genes A22110063c_transcript_59323, A22110063c_transcript_60118, A22110063c_transcript_51672 and A22110063c_transcript_48784 were highly expressed in 7#, which could be key candidate genes of alkaloid metabolism and warrant further analysis. These results provide a reference for the medicinal application of H. cordata and breeding alkaloid rich varieties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Although additive manufacturing enables controllable structural design and customized performance for magnetoelectric sensors, their design and fabrication still require careful matching of the size and modulus between the magnetic and conductive components. Achieving magnetoelectric integration remains challenging, and the rigid coils limit the flexibility of the sensors. To overcome these obstacles, this study proposes a composite process combining selective laser sintering (SLS) and 3D transfer printing for fabricating flexible liquid metal-coated magnetoelectric sensors. The liquid metal forms a conformal conductive network on the SLS-printed magnetic lattice structure. Deformation of the structure alters the magnetic flux passing through it, thereby generating voltage. A reverse model segmentation and summation method is established to calculate the theoretical magnetic flux. The impact of the volume fraction, unit size, and height of the sensors on the voltage is studied, and optimization of these factors yields a maximum voltage of 45.6 µV. The sensor has excellent sensing performance with a sensitivity of 10.9 kPa -1 and a minimum detection pressure of 0.1 kPa. The voltage can be generated through various external forces. This work presents a significant advancement in fabricating liquid metal-based magnetoelectric sensors by improving their structural flexibility, magnetoelectric integration, and design freedom., (© 2023 Wiley‐VCH GmbH.)

The protection of the replication fork structure under stress conditions is essential for genome maintenance and cancer prevention. A key signaling pathway for fork protection involves TRPV2-mediated Ca 2+ release from the ER, which is triggered after the generation of cytosolic DNA and the activation of cGAS/STING. This results in CaMKK2/AMPK activation and subsequent Exo1 phosphorylation, which prevent aberrant fork processing, thereby ensuring genome stability. However, it remains poorly understood how the TRPV2 channel is activated by the presence of cytosolic DNA. Here, through a genome-wide CRISPR-based screen, we identify TRPM8 channel-associated factor 1 (TCAF1) as a key factor promoting TRPV2-mediated Ca 2+ release under replication stress or other conditions that activate cGAS/STING. Mechanistically, TCAF1 assists Ca 2+ release by facilitating the dissociation of STING from TRPV2, thereby relieving TRPV2 repression. Consistent with this function, TCAF1 is required for fork protection, chromosomal stability, and cell survival after replication stress., (© 2024. The Author(s).)

Repairing large-area soft tissue defects caused by traumas is a major surgical challenge. Developing multifunctional scaffolds with suitable scalability and favorable cellular response is crucial for soft tissue regeneration. In this study, we developed an orthogonally woven three-dimensional (3D) nanofiber scaffold combining electrospinning, weaving, and modified gas-foaming technology. The developed orthogonally woven 3D nanofiber scaffold had a modular design and controlled fiber alignment. In vitro, the orthogonally woven 3D nanofiber scaffold exhibited adjustable mechanical properties, good cell compatibility, and easy drug loading. In vivo, for one thing, the implantation of an orthogonally woven 3D nanofiber scaffold in a full abdominal wall defect model demonstrated that extensive granulation tissue formation with enough mechanical strength could promote recovery of abdominal wall defects while reducing intestinal adhesion. Another result of diabetic wound repair experiments suggested that orthogonally woven 3D nanofiber scaffolds had a higher wound healing ratio, granulation tissue formation, collagen deposition, and re-epithelialization. Taken together, this novel orthogonally woven 3D nanofiber scaffold may provide a promising and effective approach for optimal soft tissue regeneration., Competing Interests: All authors declare no conflicts of interest in this work, and all authors have read and agreed to this submission., (© 2024 The Authors.)

Curcumin, derived from Curcuma longa (turmeric), exhibits significant potential in dermatology, addressing conditions like atopic dermatitis, psoriasis, chronic wounds, skin cancer, and infections through its anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. This review synthesizes evidence on curcumin's mechanisms, including modulation of immune responses and promotion of wound healing, showcasing its efficacy in reducing inflammation, cytokine levels, and enhancing skin barrier functions. Studies highlight curcumin's ability to selectively target tumor cells, suggesting a multifaceted approach to cancer therapy with minimal side effects. Despite promising therapeutic benefits, challenges remain in bioavailability, potency, and targeted delivery, underscoring the need for further research to optimize dosages, delivery methods, and assess long-term safety. The integration of curcumin into dermatological practice requires a balanced consideration of evidence-based efficacy and safety. Curcumin's comprehensive utility in dermatology, coupled with the necessity for advanced scientific exploration, emphasizes the importance of combining traditional knowledge with contemporary research to improve patient care in dermatology. This approach could significantly enhance outcomes for individuals with skin-related conditions, marking curcumin as a versatile and promising agent in the field., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Mo et al.)

Chronic wounds resulting from diabetes, pressure, radiation therapy, and other factors continue to pose significant challenges in wound healing. To address this, this study introduces a novel hybrid fibroin fibrous scaffold (FFS) comprising randomly arranged fibroin fibers and vertically aligned cryogel fibers (CFs). The fibroin scaffold is efficiently degummed at room temperature and simultaneously formed a porous structure. The aligned CFs are produced via directional freeze-drying, achieved by controlling solution concentration and freezing polymerization temperature. The incorporation of aligned CFs into the expanded fibroin fiber scaffold leads to enhanced cell infiltration both in vitro and in vivo, further elevating the hybrid scaffold's tissue compatibility. The anti-inflammatory peptide 1 (AP-1) is also conjugated to the hybrid fibrous scaffold, effectively transforming the inflammatory status of chronic wounds from pro-inflammatory to pro-reparative. Consequently, the FFS-AP1+CF group demonstrates superior granulation tissue formation, angiogenesis, collagen deposition, and re-epithelialization during the proliferative phase compared to the commercial product PELNAC. Moreover, the FFS-AP1+CF group displays epidermis thickness, number of regenerated hair follicles, and collagen density closer to normal skin tissue. These findings highlight the potential of random fibroin fibers/aligned CFs hybrid fibrous scaffold as a promising approach for skin tissue filling and tissue regeneration., (© 2024 Wiley‐VCH GmbH.)

Background: SIRL-1, an immunosuppressive receptor encoded by the VSTM1 gene, has recently been linked to rheumatoid arthritis (RA) due to its association with activated polymorphonuclear neutrophils (PMNs). Considering that the activated PMNs play a crucial role in the pathogenesis of rheumatoid arthritis (RA), we aimed to measure the levels of soluble SIRL-1, investigating whether they add value to RA in the clinical diagnosis., Methods: Utilizing an enzyme-linked immunosorbent assay, the concentration of sSIRL-1 was measured in serum samples from cohort 1 diagnosed with RA (n = 96), gout (n = 54), osteoarthritis (n = 47), healthy controls (n = 86) and synovial fluid samples from OA (n = 8) and RA (n = 8) patients, respectively. Additionally, an external validation in cohort 2 (n = 156) comprising various inflammatory diseases was employed., Results: The study revealed a distinctive upregulation of sSIRL-1 in the serum of RA compared to HC and other arthralgia diseases (p < 0.0001), which also displayed a significant elevation in synovial fluid from RA compared to OA (p < 0.05). Notably, sSIRL-1 levels exhibited a significant decrease in patients who achieved disease remission (p < 0.05). Furthermore, the diagnostic accuracy of RA was enhanced when sSIRL-1 was combined with anti-CCP and RF, yielding an impressive AUC value of 0.950., Conclusion: The expression pattern of sSIRL-1 in RA, coupled with its correlation with disease activity, underscores its potential clinical utility for both diagnosis and disease monitoring in RA patients. This study offers valuable insights into the evolving diagnostic landscape of RA., (Copyright © 2024. Published by Elsevier B.V.)

Anomalies in water quality, which frequently arise due to pollution, constitute a substantial menace to human health. The preservation of public welfare critically entails the timely recognition of abnormal water quality. Conventional techniques for detecting water quality anomalies face obstacles such as the necessity of expert knowledge, limited accuracy in detection, and delays in identification. In this paper, we proposed an original unsupervised technique for identifying water quality anomalies combined with time-frequency analysis and clustering (TCAD). We chose time-frequency analysis because it effectively evaluates water quality changes, generating distinct multi-band signals that reflect different aspects of water quality dynamics. We also proposed a clustering technique which can identify water quality markers and amalgamate data from multi-band signals for accurate anomaly detection. We seek to clarify the reasoning behind our methodology by portraying how time-frequency analysis and clustering address the deficiencies of conventional methods. Our experiments evaluated various indicators of water quality, and the effectiveness of our proposed approach was supported by comparative analyses with commonly used models for detecting anomalies in water quality., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Tumbling treatment is widely used in the production of cooked ham. However, traditional intermittent tumbling (IT) treatment is time-consuming. To enhance the tumbling efficiency, high-intensity ultrasound was used to assist IT treatment (UIT)., Results: UIT treatment reduced the tumbling time and significantly improved the water holding capacity, tenderness, sliceability and texture of cooked ham compared to IT treatment. Furthermore, more violent destruction of meat tissue was exhibited in the UIT treatment. This change facilitated extraction of more salt-soluble protein, which in turn welded meat pieces tightly and improved the quality of the cooked ham., Conclusion: UIT treatment could accelerate the tumbling process and enhance the quality of cooked ham. These results may provide guidance on effective strategies for a high-quality meat production process. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

The process of matching patients with suitable clinical trials is essential for advancing medical research and providing optimal care. However, current approaches face challenges such as data standardization, ethical considerations, and a lack of interoperability between Electronic Health Records (EHRs) and clinical trial criteria. In this paper, we explore the potential of large language models (LLMs) to address these challenges by leveraging their advanced natural language generation capabilities to improve compatibility between EHRs and clinical trial descriptions. We propose an innovative privacy-aware data augmentation approach for LLM-based patient-trial matching (LLM-PTM), which balances the benefits of LLMs while ensuring the security and confidentiality of sensitive patient data. Our experiments demonstrate a 7.32% average improvement in performance using the proposed LLM-PTM method, and the generalizability to new data is improved by 12.12%. Additionally, we present case studies to further illustrate the effectiveness of our approach and provide a deeper understanding of its underlying principles., (©2023 AMIA - All rights reserved.)

Clinical trials are indispensable in developing new treatments, but they face obstacles in patient recruitment and retention, hindering the enrollment of necessary participants. To tackle these challenges, deep learning frameworks have been created to match patients to trials. These frameworks calculate the similarity between patients and clinical trial eligibility criteria, considering the discrepancy between inclusion and exclusion criteria. Recent studies have shown that these frameworks outperform earlier approaches. However, deep learning models may raise fairness issues in patient-trial matching when certain sensitive groups of individuals are underrepresented in clinical trials, leading to incomplete or inaccurate data and potential harm. To tackle the issue of fairness, this work proposes a fair patient-trial matching framework by generating a patient-criterion level fairness constraint. The proposed framework considers the inconsistency between the embedding of inclusion and exclusion criteria among patients of different sensitive groups. The experimental results on real-world patient-trial and patient-criterion matching tasks demonstrate that the proposed framework can successfully alleviate the predictions that tend to be biased., (©2023 AMIA - All rights reserved.)

The extensive utilization of neonicotinoid insecticides (NNIs) in agricultural practices ultimately poses a significant threat to both the environment and human health. This work focuses on the efficient degradation and detoxification of the representative NNI, thiamethoxam (THX), and explores the underlying mechanism using a Co-Fe-Mn mixed spinel doped carbon composite catalyst activated persulfate. The findings demonstrate that the composite effectively degrades THX, achieving a degradation rate of 95% in 30 mins, while requiring only a fraction (one-sixteenth) of the oxidant dosage compared to pure carbon. The study aimed to examine the negative impact of reactive halogens on reactive oxygen species within a saline environment. The degradation byproducts were linked to the presence of two common electron-withdrawing groups, namely halogens and nitro in the THX molecule. It was hypothesized that the degradation process was primarily influenced by C-N bond breaking and hydroxylation occurring between the diazine oxide and 2-chlorothiazole rings. Consequently, dehalogenation and carbonylation processes facilitated the elimination of halogenated components and pharmacophores from the THX, leading to detoxification. In addition to the identified free radical pathway including SO 4 •- , •OH and O 2 •- contributed to THX degradation, the participation of non-radical pathways ( 1 O 2 and electron transfer) were also confirmed. The efficacy of detoxification was further validated through toxicity assessment, employing quantitative conformation relationship prediction and microbial culture utilizing Bacillus subtilis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Significant progress has been made in the development of phosphorus recovery adsorbents and photocatalysts for degradation of pesticides. However, the bifunctional materials for phosphorus recovery and photocatalytic degradation of pesticides have not been designed, and the mechanism of the interaction between photocatalysis and P adsorption remains unexplored. Herein, we develop biochar-g-C 3 N 4 -MgO composites (BC-g-C 3 N 4 -MgO) with bi-function application to minimize water toxicity and eutrophication. The results show phosphorus adsorption capacity of the BC-g-C 3 N 4 -MgO composite reaches 111.0 mg·g-1, and its degradation ratio of dinotefuran reaches 80.1% within 260 min. The mechanism studies show that MgO can play variety roles in BC-g-C 3 N 4 -MgO composite, in which can improve the adsorption capacity of phosphorus, enhance the utilization efficiency of visible light and the separation efficiency of photoinduced electron-hole pairs. The biochar existed in BC-g-C 3 N 4 -MgO serves as charge transporter with a good conductivity, which promotes the fluent transfer of photo-generated charge carriers. The ESR indicates that both •O 2 - and •OH generated from BC-g-C 3 N 4 -MgO are responsible for dinotefuran degradation. Finally, pot experiments reveal that P laden BC-g-C 3 N 4 -MgO promotes the growth of pepper seedlings with high P utilization efficiency of 49.27%., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Bacterial populations are highly adaptive. They can respond to stress and survive in shifting environments. How the behaviours of individual bacteria vary during stress, however, is poorly understood. To identify and characterize rare bacterial subpopulations, technologies for single-cell transcriptional profiling have been developed. Existing approaches show some degree of limitation, for example, in terms of number of cells or transcripts that can be profiled. Due in part to these limitations, few conditions have been studied with these tools. Here we develop massively-parallel, multiplexed, microbial sequencing (M3-seq)-a single-cell RNA-sequencing platform for bacteria that pairs combinatorial cell indexing with post hoc rRNA depletion. We show that M3-seq can profile bacterial cells from different species under a range of conditions in single experiments. We then apply M3-seq to hundreds of thousands of cells, revealing rare populations and insights into bet-hedging associated with stress responses and characterizing phage infection., (© 2023. The Author(s).)

Few researches have examined the impact of air pollution exposure during various time windows on clinical outcomes in women receiving in vitro fertilization (IVF) therapy, and the findings of studies have been conflicting. We investigated the effects of six air pollutants exposure during different time windows (period 1, 85 days before egg retrieval to the beginning of gonadotropin; period 2, the beginning of gonadotropin to egg collection; period 3, egg collection to embryo transfer; period 4, embryo transfer to serum hCG measurement; period 5, serum hCG measurement to transvaginal ultrasonography; period 6, 85 days before egg retrieval to hCG measurement; period 7, 85 days before egg retrieval to transvaginal ultrasonography) on clinical outcomes of IVF therapy. A total of seven databases were searched. NO 2 (period 6), SO 2 (period 2, 3, and 7), CO (period 1, 2 and 7) exposure were linked to lower likelihoods of clinical pregnancy. PM 2.5 (period 1), PM 10 (period 1), SO 2 (period 1, 2, 3, 4, and 6), NO 2 (period 1) were linked to lower likelihoods of biochemical pregnancy. PM 2.5 (period 1), SO 2 (period 2 and 4) and CO (period 2) were linked to reduced probabilities of live birth. Our results implied that period 1 might be the most sensitive exposure window. Air pollution exposure is linked to reduced probabilities of clinical pregnancy, biochemical pregnancy, and live birth. Therefore, preventive measures to limit air pollution exposure should be started at least three months in advance of IVF therapy to improve pregnancy outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Stroke is a significant cause of mortality and morbidity, necessitating early predictive strategies to minimize risks. Traditional methods for evaluating patients, such as Acute Physiology and Chronic Health Evaluation (APACHE II, IV) and Simplified Acute Physiology Score III (SAPS III), have limited accuracy and interpretability. This paper proposes a novel approach: an interpretable, attention-based transformer model for early stroke mortality prediction. This model seeks to address the limitations of previous predictive models, providing both interpretability (providing clear, understandable explanations of the model) and fidelity (giving a truthful explanation of the model's dynamics from input to output). Furthermore, the study explores and compares fidelity and interpretability scores using Shapley values and attention-based scores to improve model explainability. The research objectives include designing an interpretable attention-based transformer model, evaluating its performance compared to existing models, and providing feature importance derived from the model.

Background: Air pollution may impair male fertility, but it remains controversial whether air pollution affects semen quality until now., Objectives: We undertake a meta-analysis to explore potential impacts of six pollutants exposure during the entire window (0-90 days prior to ejaculation) and critical windows (0-9, 10-14, and 70-90 days prior to ejaculation) on semen quality., Methods: Seven databases were retrieved for original studies on the effects of six pollutants exposure for 90 days prior to ejaculation on semen quality. The search process does not limit the language and search date. We only included original studies that reported regression coefficients ( β ) with 95% confidence intervals (CIs). The β and 95% CIs were pooled using the DerSimonian-Laird random effect models., Results: PM 2.5 exposure was related with decreased total sperm number (10-14 lag days) and total motility (10-14, 70-90, and 0-90 lag days). PM 10 exposure was related with reduced total sperm number (70-90 and 0-90 lag days) and total motility (0-90 lag days). NO 2 exposure was related with reduced total sperm number (70-90 and 0-90 lag days). SO 2 exposure was related with declined total motility (0-9, 10-14, 0-90 lag days) and total sperm number (0-90 lag days)., Conclusion: Air pollution affects semen quality making it necessary to limit exposure to air pollution for Chinese men. When implementing protective measures, it is necessary to consider the key period of sperm development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Dai, Li, Yuan, Wang and Wang.)

Although drugs targeting the orthosteric binding site of cannabinoid receptors (CBRs) have several therapeutic effects on human physiological and pathological conditions, they can also cause serious adverse effects. Only a few orthosteric ligands have successfully passed clinical trials. Recently, allosteric modulation has become a novel option for drug discovery, with fewer adverse effects and the potential to avoid drug overdose. In this review, we highlight novel findings related to the drug discovery of allosteric modulators (AMs) targeting CBRs. We summarize newly synthesized AMs and the reported/predicted allosteric binding sites. We also discuss the structural determinants of the AMs binding as well as the molecular mechanism of CBR allostery., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The pH value within the wound microenvironment influences indirectly and directly all biochemical reactions taking place in the process of skin wound healing. Currently, it is generally believed that a low pH value, such as it is found on normal skin, is favorable for wound regeneration, while some investigations have shown that in fact alkaline microenvironments are required for some healing processes. The role of growth factors in promoting wound healing requires a specific microenvironment. In wound microenvironments of different pH, growth factors with different isoelectric points may have different effects. To explore whether the application of FGF with different isoelectric points in wounds with different pH values interferes with the healing process to different degrees, GelMA hydrogels with different pH values were prepared to maintain the wounds microenvironment with the same pH values, in which aFGF and bFGF were loaded as well. The results show that GelMA hydrogels of different pH values maintained the same pH of the wound microenvironment sustainably on the 4th day. Moreover, aFGF and bFGF promoted skin wound healing to varying degrees in different pH wound microenvironments. In particular, aFGF significantly promoted wound re-epithelialization in a weak acidic microenvironment, while bFGF promoted collagen synthesis and deposition in the early stage of weak acid wounds. In addition, aFGF plays a superior role in inhibiting inflammation in weak acidic wounds., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pan, Fan, Chen, Yuan, Chen and Cheng.)

Allosteric modulators (AMs) are considered as a perpetual hotspot in research for their higher selectivity and various effects on orthosteric ligands (OL). They are classified in terms of their functionalities as positive, negative, or silent allosteric modulators (PAM, NAM, or SAM, respectively). In the present work, 11 pairs of three-dimensional (3D) structures of receptor-orthosteric ligand and receptor-orthosteric ligand-allosteric modulator complexes have been collected for the studies, including three different systems: GPCR, enzyme, and ion channel. Molecular dynamics (MD) simulations are applied to quantify the dynamic interactions in both the orthosteric and allosteric binding pockets and the structural fluctuation of the involved proteins. Our results showed that MD simulations of moderately large molecules or peptides undergo insignificant changes compared to crystal structure results. Furthermore, we also studied the conformational changes of receptors that bound with PAM and NAM, as well as the different allosteric binding sites in a receptor. There should be no preference for the position of the allosteric binding pocket after comparing the allosteric binding pockets of these three systems. Finally, we aligned four distinct β2 adrenoceptor structures and three N -methyl-d-aspartate receptor (NMDAR) structures to investigate conformational changes. In the β2 adrenoceptor systems, the aligned results revealed that transmembrane (TM) helices 1, 5, and 6 gradually increased outward movement from an enhanced inactive state to an improved active state. TM6 endured the most significant conformational changes (around 11 Å). For NMDAR, the bottom section of NMDAR's ligand-binding domain (LBD) experienced an upward and outward shift during the gradually activating process. In conclusion, our research provides insight into receptor-orthosteric ligand-allosteric modulator studies and the design and development of allosteric modulator drugs using MD simulation.

The assessment of the health risks of volatile organic compounds (VOCs) emitted from landfills via dispersion model is crucial but also challenging because of remarkable variations in their emissions and meteorological conditions. This study used a probabilistic approach for the assessment of the health risks of typical VOCs by combining artificial neural network models for emission rates and a numerical dispersion model enhanced by probability analysis. A total of 8753 rounds of simulation were performed with distributions of waste compositions and the valid hourly meteorological conditions for 1 year. The concentration distributions and ranges of the typical health-risky VOCs after dispersion were analyzed with 95% probability. The individual and cumulative non-carcinogenic risks of the typical VOCs were acceptable with all values less than 1 in the whole study domain. For individual carcinogenic risks, only ethylbenzene, benzene, chloroform, and 1, 2-dichloroethane at extreme concentrations showed minor or moderate risks with a probability of 0.1%-1% and an impact distance of 650-3000 m at specific directions. The cumulative carcinogenic risks were also acceptable at 95% probability in the whole study domain, but exceeded 1 × 10 -6 or even 1 × 10 -4  at some extreme conditions, especially within the landfill area. The vertical patterns of the health risks with height initially increased, and then decreased rapidly, and the peak values were observed around the height of the emission source. The dispersion simulation and health risk assessment of the typical health-risky VOCs enhanced by Monte Carlo can accurately reflect their probabilistic dispersion patterns and health risks to surrounding residents from both spatial and temporal dimensions. With this approach, this study can provide important scientific basis and technical support for the health risk assessment and management of landfills., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

To advance the industrialization production of steamed buns, the current study explored the freeze-stability of unfermented, pre-fermented and par-steamed frozen dough. The results showed that the steamed bun made from unfermented dough with 2.0% yeast, the pre-fermented dough with a pre-fermented time of 30 min and the par-steamed dough with a pre-steamed time of 15 min showed the best sensory properties quality upon frozen storage. The gassing power of un- and pre-fermented dough gradually decreased, and dough with longer pre-fermented time exhibited more evident loss of gassing power. Freeze-induced depolymerization of gluten protein was the least distinct in the par-steamed dough, followed by the pre- and un-fermented dough, which was probably related to the superior freeze stability of glutenin-gliadin macro-crosslinks upon the pre-steaming stage. The surface hydrophobicity of gluten proteins of frozen dough decreased during the initial storage and was enhanced subsequently, which was related with the combined effects of the unfolding and synchronous aggregation induced by freezing and steaming, respectively. Moreover, the surface hydrophobicity of gluten in par-steamed frozen dough and steamed buns was more resistant to frozen storage, which was probably attributed to the established stable structure during the pre-steaming process.

Background: Neutrophil extracellular trap (NET) has been demonstrated to play important roles in the pathogenesis and progression of rheumatoid arthritis (RA). Emerging evidence indicates that ligation of signal inhibitory receptor on leukocytes-1 (SIRL-1) can dampen Fc receptor-induced reactive oxygen species (ROS) production in primary human neutrophils by reducing extracellular signal-regulated kinase (ERK) activation. The current study aimed to determine the regulatory effects of SIRL-1 on the NET formation and ROS production by comparing RA patients and healthy controls (HC)., Methods: Multiple assays were employed to detect the expression level of SIRL-1, including immunohistochemical staining, quantitative reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. Peripheral blood neutrophils from both HC and RA patients were freshly isolated. The NET formation was assessed spontaneously before and after exposure to serum samples from HC and RA patients, respectively. The quantification of NET formation was determined by fluorescence microscopy and Spectra Max M5 fluorescent plate reader. The ROS production was examined by flow cytometry., Results: The expression level of SIRL-1 in peripheral blood neutrophils was decreased in RA, comparing to HC. The RA-originated neutrophils showed higher levels of ROS production and NET formation. Ligation of SIRL-1 to neutrophils suppressed ROS production and NET formation. Stimulation of neutrophils with severe anti-cyclic citrullinated peptides (CCP) induced NET formation, which could be inhibited by application of SIRL-1 ligation., Conclusion: The current study identified SIRL-1 differentially expressed in neutrophils between RA and HC. Ligation of SIRL-1 inhibited ROS production and NET formation. Downregulation of SIRL-1 showed correlation with upregulation of NET formation in RA. These findings showed the regulation of SIRL-1 on NET formation and provided a potential therapeutic target for RA., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Direct production of 5-hydroxymethylfurfural (HMF) through biomass always needs the addition of exogenous catalysts and causes extra costs. Herein, acid mine drainage (AMD), one of the traditional wastewaters, was introduced as a natural catalyst to produce HMF directly from lignocellulosic biomass. Key factors in the biomass conversion were optimized and investigated by the response surface methodology (RSM), and the HMF yield reached 13.51 wt% under optimal conditions. The metal elements and the acidic environment in AMD activated the Fenton reaction to effectively destroy the lignocellulose structure and synergistically promote the formation of HMF. Furthermore, the biomass substrate in the biomass conversion was indirectly modified by the AMD during this process. The biomass conversion residue could be prepared by pyrolysis to obtain a functional metal-loaded carbon material with good adsorption of thiamethoxam (THX), which provides a sustainable solution for the disposal of biomass conversion residue., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Antibodies are essential to life, and knowing their structures can facilitate the understanding of antibody-antigen recognition mechanisms. Precise antibody structure prediction has been a core challenge for a prolonged period, especially the accuracy of H3 loop prediction. Despite recent progress, existing methods cannot achieve atomic accuracy, especially when the homologous structures required for these methods are not available. Recently, RoseTTAFold, a deep learning-based algorithm, has shown remarkable breakthroughs in predicting the 3D structures of proteins. To assess the antibody modeling ability of RoseTTAFold, we first retrieved the sequences of 30 antibodies as the test set and used RoseTTAFold to model their 3D structures. We then compared the models constructed by RoseTTAFold with those of SWISS-MODEL in a different way, in which we stratified Global Model Quality Estimate (GMQE) into three different ranges. The results indicated that RoseTTAFold could achieve results similar to SWISS-MODEL in modeling most CDR loops, especially the templates with a GMQE score under 0.8. In addition, we also compared the structures modeled by RoseTTAFold, SWISS-MODEL and ABodyBuilder. In brief, RoseTTAFold could accurately predict 3D structures of antibodies, but its accuracy was not as good as the other two methods. However, RoseTTAFold exhibited better accuracy for modeling H3 loop than ABodyBuilder and was comparable to SWISS-MODEL. Finally, we discussed the limitations and potential improvements of the current RoseTTAFold, which may help to further the accuracy of RoseTTAFold's antibody modeling., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Green tea has significant protective activity on nerve cells, but the mechanism of action is unclear. Epigallocatechin gallate (EGCG) and N -ethyl-L-glutamine (L-theanine) are the representative functional components of green tea ( Camellia sinensis ). In this study, an AD model of Aβ 25-35 -induced differentiated neural cell line PC12 cells was established to study the synergistic effect of EGCG and L-theanine in protecting neural cells. The results showed that under Aβ 25-35 stress conditions, mitochondria and axons degenerated, and the expression of cyclins was up-regulated, showing the gene and protein characteristics of cellular hyperfunction. EGCG + L-theanine inhibited inflammation and aggregate formation pathways, significantly increased the percentage of G0/G1 in the cell cycle, downregulated the expression of proteins such as p-mTOR, Cyclin D1, and Cyclin B1, upregulated the expression of GAP43, Klotho, p-AMPK, and other proteins, promoted mitochondrial activity and energy metabolism, and had repair and regeneration effects on differentiated nerve cells. The synergistic mechanism study showed that under the premise that EGCG inhibits amyloid stress and inflammation and promotes metabolism, L-theanine could play a nourish nerve effect. EGCG + L-theanine keeps differentiated nerve cells in a quiescent state, which is beneficial to the repair and regeneration of nerve cells. In addition, EGCG + L-theanine maintains the high-fidelity structure of cellular proteins. This study revealed for the first time that the synergistic effect of EGCG with L-theanine may be an effective way to promote nerve cell repair and regeneration and slow down the progression of AD. Our findings provide a new scientific basis for the relationship between tea drinking and brain protection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Wan, Zheng, Pan, Yuan, Hu, Feng, Liu and Cai.)

Allosteric modulators (AMs) that bind allosteric sites can exhibit greater selectivity than the orthosteric ligands and can either enhance agonist-induced receptor activity (termed positive allosteric modulator or PAM), inhibit agonist-induced activity (negative AM or NAM), or have no effect on activity (silent AM or SAM). Until now, it is not clear what the exact effects of AMs are on the orthosteric active site or the allosteric binding pocket(s). In the present work, we collected both the three-dimensional (3D) structures of receptor-orthosteric ligand and receptor-orthosteric ligand-AM complexes of a specific target protein. Using our novel algorithm toolset, molecular complex characterizing system (MCCS), we were able to quantify the key residues in both the orthosteric and allosteric binding sites along with potential changes of the binding pockets. After analyzing 21 pairs of 3D crystal or cryo-electron microscopy (cryo-EM) complexes, including 4 pairs of GPCRs, 5 pairs of ion channels, 11 pairs of enzymes, and 1 pair of transcription factors, we found that the binding of AMs had little impact on both the orthosteric and allosteric binding pockets. In return, given the accurately predicted allosteric binding pocket(s) of a drug target of medicinal interest, we can confidently conduct the virtual screening or lead optimization without concern that the huge conformational change of the pocket could lead to the low accuracy of virtual screening.

Although the 3D structures of active and inactive cannabinoid receptors type 2 (CB2) are available, neither the X-ray crystal nor the cryo-EM structure of CB2-orthosteric ligand-modulator has been resolved, prohibiting the drug discovery and development of CB2 allosteric modulators (AMs). In the present work, we mainly focused on investigating the potential allosteric binding site(s) of CB2. We applied different algorithms or tools to predict the potential allosteric binding sites of CB2 with the existing agonists. Seven potential allosteric sites can be observed for either CB2-CP55940 or CB2-WIN 55,212-2 complex, among which sites B, C, G and K are supported by the reported 3D structures of Class A GPCRs coupled with AMs. Applying our novel algorithm toolset-MCCS, we docked three known AMs of CB2 including Ec2la (C-2), trans-β-caryophyllene (TBC) and cannabidiol (CBD) to each site for further comparisons and quantified the potential binding residues in each allosteric binding site. Sequentially, we selected the most promising binding pose of C-2 in five allosteric sites to conduct the molecular dynamics (MD) simulations. Based on the results of docking studies and MD simulations, we suggest that site H is the most promising allosteric binding site. We plan to conduct bio-assay validations in the future.

Lower respiratory tract infections (LRTIs) are a leading cause of morbidity and mortality worldwide and lack a rapid diagnostic method. To improve the diagnosis of LRTIs, we established an available loop-mediated isothermal amplification (LAMP) assay for the detection of eight common lower respiratory pathogens, including Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Escherichia coli, Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. The whole process can be achieved within 1 h (sample to results read out). We established an extraction free isothermal system. 528 sputum samples collected from patients suspected to have LRTIs were analyzed by the system (8 tests in each sample, a total of 4224 tests) and compared with the standard culture method (SCM). The samples with inconsistent results were further verified by Sanger sequencing and High-throughput sequencing (NGS). The detection limits of the LAMP assay for the 8 pathogens ranged from 10 3 to 10 4  CFU/mL. Upon testing 528 samples, the Kappa coefficients of all pathogens ranged between 0.5 and 0.7 indicated a moderate agreement between the LAMP assay and the SCM. All inconsistent samples were further verified by Sanger sequencing, we found that the developed LAMP assay had a higher consistency level with Sanger sequencing than the SCM for all pathogens. Additionally, when the NGS was set to a diagnostic gold standard, the specificity and sensitivity of the LAMP assay for LRTIs were 94.49% and 75.00%. The present study demonstrated that the developed LAMP has high consistency with the sequencing methods. Meanwhile, the LAMP assay has a higher detection rate compared to the SCM. It may be a powerful tool for rapid and reliable clinical diagnosis of LRTIs in primary hospitals., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The design of therapeutic antibodies has attracted a large amount of attention over the years. Antibodies are widely used to treat many diseases due to their high efficiency and low risk of adverse events. However, the experimental methods of antibody design are time-consuming and expensive. Although computational antibody design techniques have had significant advances in the past years, there are still some challenges that need to be solved, such as the flexibility of antigen structure, the lack of antibody structural data and the absence of standard antibody design protocol. In the present work, we elaborated on an in silico antibody design protocol for users to easily perform computer-aided antibody design. First, the Rosetta web server will be applied to generate the 3D structure of query antibodies if there is no structural information available. Then, two-step docking will be used to identify the binding pose of an antibody-antigen complex when the binding information is unknown. ClusPro is the first method to be used to conduct the global docking, and SnugDock is applied for the local docking. Sequentially, based on the predicted binding poses, in silico alanine scanning will be used to predict the potential hotspots (or key residues). Finally, computational affinity maturation protocol will be used to modify the structure of antibodies to theoretically increase their affinity and stability, which will be further validated by the bioassays in the future. As a proof of concept, we redesigned antibody D44.1 and compared it with previously reported data in order to validate IsAb protocol. To further illustrate our proposed protocol, we used cemiplimab antibody, a PD-1 checkpoint inhibitor, as an example to showcase a step-by-step tutorial., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Conversion of the greenhouse gas CO 2 to value-added products is an important challenge for sustainable energy research. Here, a durably nanohybrid composed of Ag nanoparticles and polyacrylamide was constructed for the selectively electroreduction of CO 2 to CO. The nanohybrid exhibited an outstanding CO faradaic efficiency of 97.2±0.2 % at -0.89 V RHE (vs. the reversible hydrogen electrode) with a desirable CO partial current density of -22.0±2.3 mA cm -2 and maintained the CO faradaic efficiency above 95 % over a wide potential range (-0.79 to -1.09 V RHE ), showing excellent stability during a 48 h prolonged electrolysis. The origins of selective enhancement of CO 2 reduction over the nanohybrid stemmed from the activation of CO 2 via hydrogen bond and the low basicity of the amide. DFT calculations implied that the synergy of Ag nanoparticles and amide could better stabilize the key intermediate (*COOH) and effectively lower the overpotential of CO 2 reduction. These results establish the synergistic effects of organic/inorganic hybrid as a complementary method for tuning selectivity in CO 2 -to-fuels catalysis., (© 2020 Wiley-VCH GmbH.)

Helical elements separated by bulges frequently undergo transitions between unstacked and coaxially stacked conformations during the folding and function of noncoding RNAs. Here, we examine the dynamic properties of poly-pyrimidine bulges of varying length ( n = 1-4, 7) across a range of Mg 2+ concentrations using HIV-1 TAR RNA as a model system and solution NMR spectroscopy. In the absence of Mg 2+ , helices linked by bulges with n ≥ 3 residues adopt predominantly unstacked conformations (stacked population <15%), whereas one-bulge and two-bulge motifs adopt predominantly stacked conformations (stacked population >74%). In the presence of 3 mM Mg 2+ , the helices predominantly coaxially stack (stacked population >84%), regardless of bulge length, and the midpoint for the Mg 2+ -dependent stacking transition is within threefold regardless of bulge length. In the absence of Mg 2+ , the difference between free energy of interhelical coaxial stacking across the bulge variants is estimated to be ∼2.9 kcal/mol, based on an NMR chemical shift mapping with stacking being more energetically disfavored for the longer bulges. This difference decreases to ∼0.4 kcal/mol in the presence of Mg 2+ NMR RDCs and resonance intensity data show increased dynamics in the stacked state with increasing bulge length in the presence of Mg 2+ We propose that Mg 2+ helps to neutralize the growing electrostatic repulsion in the stacked state with increasing bulge length thereby increasing the number of coaxial conformations that are sampled. Energetically compensated interhelical stacking dynamics may help to maximize the conformational adaptability of RNA and allow a wide range of conformations to be optimally stabilized by proteins and ligands., (© 2018 Merriman et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Nanoparticles (NPs) have demonstrated a potential for hepatocarcinoma therapy. However, the effective and safe NP-mediated drug transportation is still challenging due to premature leakage and inaccurate release of the drug. Herein, we designed a series of core cross-linking galactose-based glycopolymer-drug conjugates (GPDs) NPs with both redox-responsive and pH-sensitive characteristics to target and program drug release. Glycopolymer is comprised of galactose-containing units, which gather on the surface of GPD NPs and exhibit specific recognition to hepatocarcinoma cells, which over-express the asialoglycoprotein receptor. GPD NPs are stable in a normal physiological environment and can rapidly release the drug in hepatocarcinoma cells, which are reductive and acidic, by combining disulfide bond cross-linked core, as well as boronate ester-linked hydrophilic glycopolymer chain and the hydrophobic drug.

The high metastatic potential of non-small cell lung cancers (NSCLCs) is closely correlated with the elevated expression of vascular endothelial growth factor (VEGF) and resultant tumor angiogenesis. However, no effective strategies against VEGF expression have been available in NSCLCs therapy. This study demonstrated that elevated reactive oxygen species (ROS) levels derived from both mitochondria and NADPH oxidase were required for VEGF expression in NSCLC cells. Atorvastatin administration could significantly inhibit VEGF expression both in vitro and in vivo via inhibition of ROS production. Atorvastatin inhibited ROS generation partly through suppression of Rac1/NADPH oxidase activity. Specifically, atorvastatin could upregulate the activity of glutathione peroxidase (GPx) and catalase, which are responsible for elimination of hydrogen peroxide (H(2)O(2)) in the mitochondria and peroxisomes, respectively. Thus, inhibition of ROS production by concomitant suppression of Rac1/NADPH oxidase activity and upregulation of the activity of GPx and catalase contributes critically to atorvastatin-reduced VEGF expression in NSCLCs. Atorvastatin may be a potential alternative against VEGF expression and angiogenesis in NSCLCs therapy., (Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Studies towards the synthesis of the macrocyclic core of (-)-zampanolide are reported. The synthetic approach features a one-pot reduction/vinylogous aldol reaction for construction of the C15-C20 fragment, an intramolecular silyl-modified Sakurai (ISMS) reaction for construction of the 2,6- cis -disubstituted exo -methylene pyran subunit, and use of an sp 2 -sp 3 Stille reaction for macrocyclization.