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Background: Trans-oral robotic surgery (TORS) and trans-oral laser microsurgery (TLM) have been increasingly employed for the diagnosis and identification of primary occult cancers in the head and neck region. This systematic review and meta-analysis aimed to evaluate the application and effectiveness of tonsillectomy with TORS and TLM in detecting these cancers., Methods: We searched PubMed, EMBASE, and the Cochrane Library for eligible studies using TORS or TLM in identifying the unknown primary sites of occult head and neck cancer, published from inception to September 2023. Two investigators independently screened articles based on inclusion and exclusion criteria., Results: From 2282 articles identified, 20 individual studies meeting the inclusion criteria were included in this meta-analysis. Primary tumors were identified by TORS/TLM in 65% (364/561) of patients. The initial identification rates of lingual tonsillectomy (n = 219) and palatine tonsillectomy (n = 83) were 39% and 15%, respectively. The identification rates of primary sites for trans-oral surgical techniques were 60.7% (95% CI, 49.4-72%) for TORS and 75.7% (95% CI, 60.7-90.7%) for TLM. Seventy-nine point six percent (467/587) of the tumors were associated with human papilloma virus (HPV). The detection rate of HPV+ tumors was 79% (173/220) and the detection rate of HPV- tumors was 10% (5/52). The most common complication was nasogastric/gastrostomy, accounting for 6% (29/481). The length of hospital stay reported varied from 1 to more than 7 days., Conclusion: This is a latest systematic review of the detection rates of head and neck squamous cell carcinoma of unknown primary sites by tongue base mucosectomy (TBM) via TORS and TBM via TLM. This study confirmed that TBM via TLM performed better than TBM-TORS in the detection rate of the primary. In particular, TBM via TLM showed significant advantages in detecting primary lesions in HPV-positive head and neck squamous cell carcinoma of unknown primary patients., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Bioaerosols have attracted increasing attention as novel contaminants because of their potential role in the spread of disease. In this study, sampling sites were established in a landfill in northwestern China with the aim of investigating the emission and diffusion characteristics of bioaerosols. The results revealed that the counts of airborne bacteria released by landfill cover area (LCA) and waste dumping area (WDA) located in the landfill area reached 18 193 ± 30 CFU/m 3 and 10 948 ± 105 CFU/m 3 , respectively. These two aeras were the main sources of bioaerosol generation. Meanwhile, Corynebacterium spp., Bacteroidetes spp., and Pseudomonas spp. were identified as potential pathogens. A Gaussian model was applied to simulate the diffusion of the bioaerosols; the influence distance was calculated as 12 km from the boundary of the landfill site. The potential health risks of bioaerosol exposure to on-site workers and nearby residents were calculated and evaluated in terms of aerosol concentration, particle size, and pathogenic bacteria. The present study promotes the recognition of the emission behavior of microorganisms in aerosol particles and provides a basis for controlling bioaerosol contamination from landfill sites, particularly those located in cold and arid northwestern regions of China., 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.)

Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme in the salvaging synthesize pathway of nicotinamide adenine dinucleotide (NAD). The neuroprotective roles of NAMPT on neurodegeneration have been explored in aging brain and Alzheimer's Disease. However, its roles in Parkinson's Disease (PD) remain to be elucidated. We found that the dopaminergic neurons in substantia nigra expressed higher levels of NAMPT than the other types of neurons. Using conditional knockout of the Nampt gene in dopaminergic neurons and utilizing a NAMPT inhibitor in the substantia nigra of mice, we found that the NAMPT deficiency triggered the time-dependent loss of dopaminergic neurons, the impairment of the dopamine nigrostriatal pathway, and the development of PD-like motor dysfunction. In the rotenone-induced PD mouse model, nicotinamide ribose (NR), a precursor of NAD, rescued the loss of dopaminergic neurons, the impairment of dopamine nigrostriatal pathway, and mitigated PD-like motor dysfunction. In SH-SY5Y cells, NAD suppression induced the accumulation of reactive oxygen species (ROS), mitochondrial impairment, and cell death, which was reversed by N-acetyl cysteine, an antioxidant and ROS scavenger. Rotenone decreased NAD level, induced the accumulation of ROS and the impairment of mitochondria, which was reversed by NR. In summary, our findings show that the ablation of NAMPT in dopaminergic neurons leads to neurodegeneration and contributes to the development of PD. The NAD precursors have the potential to protect the degeneration of dopaminergic neurons, and offering a therapeutic approach for the treatment of PD., 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. Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Primary diffuse large B-cell lymphoma of the bone (PB-DLBCL) is an extremely rare type of extra-nodal lymphoma. The clinical characteristics, management, and survival outcomes of adult PB-DLBCL patients remain poorly defined. To explore the clinical manifestations, staging, therapeutic options, prognostic factors and outcomes of adult patients with PB-DLBCL and to create a model to predict survival outcomes. Data of adult PB-DLBCL patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program 18 registries database from 2000 to 2018. The Kaplan-Meier survival analysis was conducted to calculate survival rates. Univariate Cox regression, best subset selection (BESS), and least absolute shrinkage and selection operator (LASSO), followed by backward stepwise multivariable Cox regression, were used to construct the nomogram. The nomograms were evaluated using the concordance index (C-index), calibration curves and decision curve analysis (DCA). Diffuse large B-cell lymphoma (DLBCL) (67.51%) was the most frequent type of primary bone lymphoma. The most involved sites were the spine and lower-limb long bones. For the whole cohort, the 3-, 5-, 10- and 15-year overall survival (OS) rates were 74.9%, 70.5%, 60.0%, and 49.9%, and corresponding disease-specific survival (DSS) rates were 79.7%, 77.8%, 75.1%, and 71.4%, respectively. For OS, age, Ann Arbor stage, primary site and therapy were confirmed as final factors to develop the nomogram in adult PB-DLBCL patients, whereas for DSS, Age, marital status, Ann Arbor stage, number of bone lesions, therapy and year of diagnosis were confirmed as final factors in developing the nomogram. The nomograms demonstrated good accuracy and clinical utility. Established nomograms can accurately predict the survival of patients with PB-DLBCL and help clinicians optimize treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Wastewater treatment plants (WWTPs) are major sources of volatile gaseous compounds, especially in mixed-source systems such as domestic wastewater and landfill leachate. This study aimed to investigate the emission behavior and environmental impact of gaseous substances, such as hydrogen sulfide (H 2 S), ammonia (NH 3 ), carbon sulfide (CS 2 ), and phosphine (PH 3 ), at a WWTP in Northwest China. Odorants were detected in the air surrounding the grid room (XGS), biochemical treatment tank (SHC), secondary sedimentation tank (ECC), and sludge dewatering room (NTS). For comparison, the upwind boundary (O-SF) and downwind boundaries (O-XF) monitoring points were used, with odor concentrations ranging from 3.95 to 725.27 odor units. The concentration ranges of the odorant substances were 5.27-88.69, 5.61-71.96, 5.70-32.63, and 0.12-5.87 mg/m 3 for H 2 S, NH 3 , CS 2 , and PH 3 , respectively. Meteorological factors such as temperature, relative humidity, and wind speed and direction substantially influence odorant emissions. The concentrations of various odorants and volatile organic compounds (VOCs) detected at the O-XF monitoring point were higher than those detected at the O-SF monitoring point, indicating that the wind intensified their diffusion toward the downwind plant boundary. The average odor intensities of odorant substances emitted from wastewater or sludge treatment equipment were 3.37, 5.09, 4.42, 2.00, and 3.82 for total VOCs, H 2 S, NH 3 , CS 2 , and PH 3 , respectively. Among them four, with downwind diffusion, only H 2 S presented olfactory and chronic toxicity risks based on Gaussian plume model calculations. The hazard index ranking across monitoring sites was XGS > NTS > SHC > ECC > O-XF > O-SF. These findings emphasize the urgent need for effective measures to control and mitigate gaseous pollutants emitted by collaborative WWTPS, thereby protecting environmental quality and public health., 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 Ltd. All rights reserved.)

Cytotherapy is a strategy to deliver modified cells to a diseased tissue, but targeting solid tumours remains challenging. Here we design macrophages, harbouring a surface glypican-3-targeting peptide and carrying a cargo to combat solid tumours. The anchored targeting peptide facilitates tumour cell recognition by the engineered macrophages, thus enhancing specific targeting and phagocytosis of tumour cells expressing glypican-3. These macrophages carry a cargo of the TLR7/TLR8 agonist R848 and INCB024360, a selective indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, wrapped in C16-ceramide-fused outer membrane vesicles (OMV) of Escherichia coli origin (RILO). The OMVs facilitate internalization through caveolin-mediated endocytosis, and to maintain a suitable nanostructure, C16-ceramide induces membrane invagination and exosome generation, leading to the release of cargo-packed RILOs through exosomes. RILO-loaded macrophages exert therapeutic efficacy in mice bearing H22 hepatocellular carcinomas, which express high levels of glypican-3. Overall, we lay down the proof of principle for a cytotherapeutic strategy to target solid tumours and could complement conventional treatment., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer often associated with chronic hepatitis B virus infection (CHB) and liver cirrhosis (LC), underscoring the critical need for biomarker discovery to improve patient outcomes. Emerging as a promising avenue for biomarker development, proteomic technology leveraging liquid biopsy from small extracellular vesicles (sEV) offers new insights. Here, we evaluated various methods for sEV isolation and identified polysaccharide chitosan (CS) as an optimal approach. Subsequently, we employed optimized CS-based magnetic beads (Mag-CS) for sEV separation from serum samples of healthy controls, CHB, LC, and HBV-HCC patients. Leveraging data-independent acquisition mass spectrometry coupled with machine learning, we uncovered potential vesicular protein biomarker signatures (KNG1, F11, KLKB1, CAPNS1, CDH1, CPN2, NME2) capable of distinguishing HBV-HCC from CHB, LC, and non-HCC conditions. Collectively, our findings highlight the utility of Mag-CS-based sEV isolation for identifying early detection biomarkers in HBV-HCC., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Introduction: Guillain-Barré syndrome (GBS) is a monophasic immune neuropathic disorder characterized by acute paralysis. A significant portion of patients are left with residual deficits, which presents a considerable global healthcare challenge. The precise mechanisms underlying GBS pathogenesis are not fully elucidated. Recent studies have focused on postinfectious molecular mimicry and identified involvement of IgG autoantibodies and innate immune effectors in GBS. Intravenous immunoglobulins (IVIg) and plasma exchange (PE) are two established evidence-based immunomodulatory treatments for GBS, but a significant proportion of GBS patients fails to respond adequately to either therapy. This emphasizes an urgent need for novel and more potent treatments., Areas Covered: We discuss novel immunomodulatory therapies presently at different phases of preclinical and clinical investigation. Some drugs in development target pathophysiologic mechanisms such as IgG autoantibody catabolism and complement activation, which are relevant to GBS., Expert Opinion: There is an unmet need for more effective immune therapies for GBS. New immunomodulatory therapies under development may provide more potent options for GBS patients who do not respond to IVIg or PE. Future directions may include incorporating neuroprotective interventions based on evolving understanding of mechanisms underlying nerve injury and axonal degeneration.

Pancreatic ductal adenocarcinoma (PDAC) poses a formidable challenge in oncology due to its limited treatment options and poor long-term survival rates. Our previous work identified MG53, a member of the tripartite motif family protein (TRIM72), as a key player in tissue repair with potential applications in regenerative medicine. Despite the focus on MG53's cytosolic functions, its nuclear role in suppressing pancreatic cancer remains unknown. Through orthotopic and subcutaneous transplantation studies in mice, we observed enhanced tumor growth in MG53-deficient mice compared to wild-type counterparts. The overexpression of KIF11, a motor protein crucial for cell mitosis regulation, has been linked to the aggressive proliferation of pancreatic cancer cells. Confocal imaging confirmed MG53's presence in the nucleus of human pancreatic cancer cells, while functional assays demonstrated its impact on KIF11 expression and subsequent cell proliferation. Mechanistically, we revealed MG53's transcriptional control over KIF11, leading to cell cycle arrest. Our findings position MG53 as a promising tumor suppressor in PDAC, offering a novel avenue for therapeutic intervention by regulating KIF11 expression., Competing Interests: Declaration of competing interest Dr. Jianjie Ma (J.M.) is founder of TRIM-edicine, which develops MG53 for the treatment of human disease. Patents on the use of MG53 are held by Rutgers University-Robert Wood Johnson Medical School and The Ohio State University., (Copyright © 2024. Published by Elsevier Inc.)

The circulation of tumor cells through the bloodstream is a significant step in tumor metastasis. To better understand the metastatic process, circulating tumor cell (CTC) survival in the circulation must be explored. While immune interactions with CTCs in recent decades have been examined, research has yet to sufficiently explain some CTC behaviors in blood flow. Studies related to CTC mechanical responses in the bloodstream have recently been conducted to further study conditions under which CTCs might die. While experimental methods can assess the mechanical properties and death of CTCs, increasingly sophisticated computational models are being built to simulate the blood flow and CTC mechanical deformation under fluid shear stresses (FSS) in the bloodstream.Several factors contribute to the mechanical deformation and death of CTCs as they circulate. While FSS can damage CTC structure, diverse interactions between CTCs and blood components may either promote or hinder the next metastatic step-extravasation at a remote site. Overall understanding of how these factors influence the deformation and death of CTCs could serve as a basis for future experiments and simulations, enabling researchers to predict CTC death more accurately. Ultimately, these efforts can lead to improved metastasis-specific therapeutics and diagnostics specific in the future., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

CRISPR/Cas-based transcriptional activators can be enhanced by intrinsically disordered regions (IDRs). However, the underlying mechanisms are still debatable. Here, we examine 12 well-known IDRs by fusing them to the dCas9-VP64 activator, of which only seven can augment activation, albeit independently of their phase separation capabilities. Moreover, modular domains (MDs), another class of multivalent molecules, though ineffective in enhancing dCas9-VP64 activity on their own, show substantial enhancement in transcriptional activation when combined with dCas9-VP64-IDR. By varying the number of gRNA binding sites and fusing dCas9-VP64 with different IDRs/MDs, we uncover that optimal, rather than maximal, cis-trans cooperativity enables the most robust activation. Finally, targeting promoter-enhancer pairs yields synergistic effects, which can be further amplified via enhancing chromatin interactions. Overall, our study develops a versatile platform for efficient gene activation and sheds important insights into CRIPSR-based transcriptional activators enhanced with multivalent molecules., (© 2024. The Author(s).)

Hypothyroidism is commonly detected in patients with medulloblastoma (MB). However, whether thyroid hormone (TH) contributes to MB pathogenicity remains undetermined. Here, we find that TH plays a critical role in promoting tumor cell differentiation. Reduction in TH levels frees the TH receptor, TRα1, to bind to EZH2 and repress expression of NeuroD1, a transcription factor that drives tumor cell differentiation. Increased TH reverses EZH2-mediated repression of NeuroD1 by abrogating the binding of EZH2 and TRα1, thereby stimulating tumor cell differentiation and reducing MB growth. Importantly, TH-induced differentiation of tumor cells is not restricted by the molecular subgroup of MB, suggesting that TH can be used to broadly treat MB subgroups. These findings establish an unprecedented association between TH signaling and MB pathogenicity, providing solid evidence for TH as a promising modality for MB treatment., Competing Interests: Declaration of interests A patent related to this work has been filed by Fox Chase Cancer Center (Yang Y.J. and Yang Z.J.)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Liquid-liquid phase separation (LLPS) is the mechanism underlying the formation of bio-molecular condensates which are important compartments regulating intra- and extra-cellular functions. Electrostatic interactions are some of the important driving forces of the LLPS behaviors of biomolecules. However, the understanding of the electrostatic interactions is still limited, especially in the mixtures of biomolecules with different charge patterns. Here, we focus on the electrostatic interactions in mixtures of charge-asymmetric and charge-symmetric polyampholytes and their roles in the phase separation behaviors. We build charge-asymmetric and charge-symmetric model proteins consisting of both glutamic acid (E, negatively charged) and lysine (K, positively charged), i.e. polyampholytes of E 35 K 15 (charge asymmetric) and E 25 K 25 (charge symmetric). Pure E 25 K 25 can undergo LLPS. To investigate the effects of charge-asymmetric polyampholytes on the mixtures of E 25 K 25 /E 35 K 15 , we perform coarse-grained simulations to determine their phase separation. The charge-asymmetric polyampholyte E 35 K 15 is resistant to the LLPS of the mixtures of E 25 K 25 /E 35 K 15 . The condensate density decreases with the molar fraction of E 35 K 15 increasing to 0.4, and no LLPS occurs at the molar fraction of 0.5 and above. This can be attributed to the electrostatic repulsion between the negatively charged E 35 K 15 polymers. We further investigate the effects of charge asymmetry on the conformations and properties of the condensates. The E 35 K 15 polymers in the condensates exhibit a more collapsed state as the molar fraction of E 35 K 15 increases. However, the conformation of E 25 K 25 polymers changes slightly across different condensates. The surface tensions of condensates decline with the increase of the molar fraction of E 35 K 15 polymers, while the diffusivity of polymers in the condensed phases is enhanced. This work elucidates the role of charge-asymmetric polyampholytes in determining the LLPS behaviours of binary mixtures of charge-symmetric and charge-asymmetric proteins as well as the properties of condensed phases.

Volatile organic compounds emitted from landfills posed adverse effect on health. In this study, gaseous benzene was biologically treated using an in-situ biofilter without air pump. Its performance was investigated and the removal efficiency of benzene reached over 90 %. The decrease in the average benzene concentration was consistent with first-order reaction kinetics. Mycolicibacterium dominated the bacterial consortium (41-57 %) throughout the degradation. Annotation of genes by metagenomic analysis helped to deduce the degradation pathways (benzene degradation, catechol ortho-cleavage and meta-cleavage) and to reveal the contribution of different species to the degradation process. In total, 21 kinds of key genes and 13 enzymes were involved in the three modules of benzene transformation. Mycolicibacter icosiumassiliensis and Sphingobium sp. SCG-1 carried multiple functional genes critically involved in benzene biodegradation. These findings provide technical and theoretical support for the in-situ bioremediation of benzene-contaminated soil and waste gas reduction in 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 © 2024 Elsevier Ltd. All rights reserved.)

The three-dimensional (3D) organization of chromatin within the nucleus is crucial for gene regulation. However, the 3D architectural features that coordinate the activation of an entire chromosome remain largely unknown. We introduce an omics method, RNA-associated chromatin DNA-DNA interactions, that integrates RNA polymerase II (RNAPII)-mediated regulome with stochastic optical reconstruction microscopy to investigate the landscape of noncoding RNA roX2 -associated chromatin topology for gene equalization to achieve dosage compensation. Our findings reveal that roX2 anchors to the target gene transcription end sites (TESs) and spreads in a distinctive boot-shaped configuration, promoting a more open chromatin state for hyperactivation. Furthermore, roX2 arches TES to transcription start sites to enhance transcriptional loops, potentially facilitating RNAPII convoying and connecting proximal promoter-promoter transcriptional hubs for synergistic gene regulation. These TESs cluster as roX2 compartments, surrounded by inactive domains for coactivation of multiple genes within the roX2 territory. In addition, roX2 structures gradually form and scaffold for stepwise coactivation in dosage compensation.

Investigations concerning the glyoxylate moiety as a photocleavable functional group for visible light photoinitiators, particularly in the initiation of free radical photopolymerization remain limited. This study introduces nine innovative carbazole-based ethyl glyoxylate derivatives (CEGs), which are synthesized and found to exhibit excellent photoinitiation abilities as monocomponent photoinitiating systems. Notably, these structures demonstrate robust absorption in the near-UV/visible range, surpassing the commercial photoinitiators. Moreover, the newly developed glyoxylate derivatives show higher acrylate function conversions compared to a benchmark photoinitiator (MBF) in free radical photopolymerization. Elucidation of the photoinitiation mechanism of CEGs is achieved through a comprehensive analysis involving the decarboxylation reaction and electron spin resonance spin trapping. Furthermore, their practical utility is confirmed during direct laser writing and 3D printing processes, enabling the successful fabrication of 3D printed objects. This study introduces pioneering concepts and effective strategies in the molecular design of novel photoinitiators, showcasing their potential for highly advantageous applications in 3D printing., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Background: Fibrolipoma of the lower lip is an uncommon condition with limited documentation in the literature. This paper provides updated insights into oral and maxillofacial lipomas through a detailed case report and comprehensive literature review, discussing clinical features, pathogenesis, diagnostic approaches, histopathology, and therapeutic strategies., Case Presentation: A 54-year-old female presented with a painless, enlarging mass on the inner aspect of her right lower lip, first noticed 2 years prior. The mass, now the size of a peanut, interfered with her eating and speech. Physical examination revealed a 2.0 × 2.5 × 1.0 cm mass beneath the mucous membrane of the right lower lip. It was firm, well-demarcated, and mobile. Surgical excision was performed, and histopathological analysis confirmed the diagnosis of a lower lip fibrolipoma. The lesion was successfully removed without recurrence., Conclusion: Lipomas in the oral and maxillofacial regions are rare, slow-growing benign tumors, particularly within the lips. Although their diagnosis is straightforward based on clinical presentation, histopathological confirmation is essential. Surgical resection remains the treatment of choice, with excellent prognostic outcomes., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Sprouty-related enabled/vasodilator-stimulated phosphoprotein homology 1 domain containing 2 (SPRED2) is an inhibitor of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and has been shown to promote autophagy in several cancers. Here, we aimed to determine whether SPRED2 plays a role in autophagy in hepatocellular carcinoma (HCC) cells. The Cancer Genome Atlas (TCGA) Liver Cancer Database showed a negative association between the level of SPRED2 and p62, a ubiquitin-binding scaffold protein that accumulates when autophagy is inhibited. Immunohistochemically, accumulation of p62 was detected in human HCC tissues with low SPRED2 expression. Overexpression of SPRED2 in HCC cells increased the number of autophagosomes and autophagic vacuoles containing damaged mitochondria, decreased p62 levels, and increased levels of light-chain-3 (LC3)-II, an autophagy marker. In contrast, SPRED2 deficiency increased p62 levels and decreased LC3-II levels. SPRED2 expression levels were negatively correlated with translocase of outer mitochondrial membrane 20 (TOM20) expression levels, suggesting its role in mitophagy. Mechanistically, SPRED2 overexpression reduced ERK activation followed by the mechanistic or mammalian target of rapamycin complex 1 (mTORC1)-mediated signaling pathway, and SPRED2 deficiency showed the opposite pattern. Finally, hepatic autophagy was impaired in the liver of SPRED2-deficient mice with hepatic lipid droplet accumulation in response to starvation. These results indicate that SPRED2 is a critical regulator of autophagy not only in HCC cells, but also in hepatocytes, and thus the manipulation of this process may provide new insights into liver pathology.

Peripheral nerve injury (PNI) resulting from trauma or neuropathies can cause significant disability, and its prognosis deteriorates with age. Emerging evidence suggests that gut dysbiosis and reduced fecal short-chain fatty acids (SCFAs) contribute to an age-related systemic hyperinflammation (inflammaging), which hinders nerve recovery after injury. This study thus aimed to evaluate the pro-regenerative effects of a rejuvenating fecal microbiota transplant (FMT) in a preclinical PNI model using aged mice. Aged C57BL/6 mice underwent bilateral crush injuries to their sciatic nerves. Subsequently, they either received FMT from young donors at three and four days after the injury or retained their aged gut microbiota. We analyzed gut microbiome composition and SCFA concentrations in fecal samples. The integrity of the ileac mucosal barrier was assessed by immunofluorescence staining of Claudin-1. Flow cytometry was utilized to examine immune cells and cytokine production in the ileum, spleen, and sciatic nerve. Various assessments, including behavioural tests, electrophysiological studies, and morphometrical analyses, were conducted to evaluate peripheral nerve function and repair following injury. Rejuvenating FMT reversed age-related gut dysbiosis by increasing Actinobacteria, especially Bifidobacteriales genera. This intervention also led to an elevation of gut SCFA levels and mitigated age-related ileac mucosal leakiness in aged recipients. Additionally, it augmented the number of T-helper 2 (Th2) and regulatory T (Treg) cells in the ileum and spleen, with the majority being positive for anti-inflammatory interleukin-10 (IL-10). In sciatic nerves, rejuvenating FMT resulted in increased M2 macrophage counts and a higher IL-10 production by IL-10 + TNF-α - M2 macrophage subsets. Ultimately, restoring a youthful gut microbiome in aged mice led to improved nerve repair and enhanced functional recovery after PNI. Considering that FMT is already a clinically available technique, exploring novel translational strategies targeting the gut microbiome to enhance nerve repair in the elderly seems promising and warrants further evaluation., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Advances in medical technology have enabled minimally invasive treatment of type A aortic dissection with accompanying aortic regurgitation. Implants include endovascular stent grafts (ESG) and heart valve substitute (HVS) modules. Traditional implants can be divided into two types based on the assembly relationship between ESG and HVS: separated z-shaped implants (SZ) and separated diamond-shaped implants (SD). This study proposes a novel linked diamond-shaped implant (LD). To evaluate the safety and effectiveness of this new implant, finite element simulation models were created to assess the risks of endoleak, migration, and vascular wall rupture under annulus displacement load. After the SZ, SD, and LD implants were grafted in virtual release method, all the implants can cover tear-entry located in the ascending aorta, but space distance ( δ ) which exposed to blood was 14.5, 13.1, and 7.4 mm, respectively; the maximum areas of contact gap was 76.5, 51.5 and 6.3 mm 2 ; the maximum migration distance (ΔL1) were 1.27, 1.06, and 0.1 mm; the maximum stress on ascending aorta was 0.19, 0.24, and 0.51 MPa, which were lower than failure stress (0.9 MPa). This study showed that both SZ and SD implants had minimal effects on the ascending aorta; however, higher risks were associated with implant migration and proximal endoleak. In contrast, the LD implant can simplify the surgical procedure, has a lower risk of endoleak and migration, and limited stress stimulation of the aorta. This study validated the feasibility and effectiveness of this novel implant using the finite element method, indicating its potential as a secure and reliable treatment option.

Effective presentation of antigens by dendritic cells (DC) is essential for achieving a robust cytotoxic T lymphocytes (CTLs) response, in which cDC1 is the key DC subtype for high-performance activation of CTLs. However, low cDC1 proportion, complex process, and high cost severely hindered cDC1 generation and application. Herein, the study proposes an in situ cDC1 recruitment and activation strategy with simultaneous inhibiting cancer stemness for inducing robust CTL responses and enhancing the anti-tumor effect. Fms-like tyrosine kinase 3 ligand (FLT3L), Poly I:C, and Nap-CUM (NCUM), playing the role of cDC1 recruitment, cDC1 activation, inducing antigen release and decreasing tumor cell stemness, respectively, are co-encapsulated in an in situ hydrogel vaccine (FP/NCUM-Gel). FP/NCUM-Gel is gelated in situ after intra-tumoral injection. With the near-infrared irradiation, tumor cell immunogenic cell death occurred, tumor antigens and immunogenic signals are released in situ. cDC1 is recruited to tumor tissue and activated for antigen cross-presentation, followed by migrating to lymph nodes and activating CTLs. Furthermore, tumor cell stemness are inhibited by napabucasin, which can help CTLs to achieve comprehensive tumor killing. Collectively, the proposed strategy of cDC1 in situ recruitment and activation combined with stemness inhibition provides great immune response and anti-tumor potential, providing new ideas for clinical tumor vaccine design., (© 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Here, 0.3 wt.%Zr was introduced in an Al-4 wt.%Cu-0.5 wt.%Mn-0.1 wt.%Fe alloy to investigate its influence on the microstructure and mechanical properties of the alloy. The microstructures of both as-cast and T6-treated Al-Cu-Mn-Fe (ACMF) and Al-Cu-Mn-Fe-Zr (ACMFZ) alloys were analyzed. The intermetallic compounds formed through the casting procedure include Al 2 Cu and Al 7 Cu 2 Fe, and the Al 2 Cu phase dissolves into the matrix and re-precipitates as θ' phase during the T6 process. The introduction of Zr results in the precipitation of L1 2 -Al 3 Zr nanometric precipitates after T6, while the θ' precipitates in ACMFZ alloy are much finer than those in ACMF alloy. The L1 2 -Al 3 Zr precipitates were found coherently located with θ', which was assumed beneficial for stabilizing the θ' precipitates during the high-temperature tensile process. The tensile properties of ACMF and ACMFZ alloys at room temperature and elevated temperatures (200, 300, and 400 °C) were tested. Especially, the yield strength of ACMFZ alloys can reach 128 MPa and 65 MPa at 300 °C and 400 °C, respectively, which are 31% and 33% higher than those of ACMF alloys. The strengthening mechanisms of grain size, L1 2 -Al 3 Zr, and θ' precipitates on the tensile properties were discussed. This work may be referred to for designing Al-Cu alloys for application in high-temperature fields.

Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have shown encouraging clinical benefits for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC). Nevertheless, therapeutic efficacy and wide clinical applicability remain a challenge due to "cold" tumors' immunological characteristics. Tumor immunosuppressive microenvironment (TIME) continuously natural force for immune escape by extracellular matrix (ECM) infiltration, tumor angiogenesis, and tumor cell proliferation. Herein, we proposed a novel concept by multi-overcoming immune escape to maximize the ICIs combined with antiangiogenic therapy efficacy against HCC. A self-delivery photothermal-boosted-NanoBike (BPSP) composed of black phosphorus (BP) tandem-augmented anti-PD-L1 mAb plus sorafenib (SF) is meticulously constructed as a triple combination therapy strategy. The simplicity of BPSP's composition, with no additional ingredients added, makes it easy to prepare and presents promising marketing opportunities. (1) NIR-II-activated BPSP performs photothermal therapy (PTT) and remodels ECM by depleting collagen I, promoting deep penetration of therapeutics and immune cells. (2) PTT promotes SF release and SF exerts anti-vascular effects and down-regulates PD-L1 via RAS/RAF/ERK pathway inhibition, enhancing the efficacy of anti-PD-L1 mAb in overcoming immune evasion. (3) Anti-PD-L1 mAb block PD1/PD-L1 recognition and PTT-induced ICD initiates effector T cells and increases response rates of PD-L1 mAb. Highly-encapsulated BPSP converted 'cold' tumors into 'hot' ones, improved CTL/Treg ratio, and cured orthotopic HCC tumors in mice. Thus, multi-overcoming immune escape offers new possibilities for advancing immunotherapies, and photothermal/chemical/immune synergistic therapy shows promise in the clinical development of HCC., (© 2024. The Author(s).)

Lignin accumulation can enhance the disease resistance of young tea shoots ( Camellia sinensis ). It also greatly reduces their tenderness, which indirectly affects the quality and yield of tea. Therefore, the regulation of lignin biosynthesis appears to be an effective way to balance tenderness and disease resistance in young tea shoots. In this study, we identified a laccase gene, CsLAC17 , that is induced during tenderness reduction and gray blight infection in young tea shoots. Overexpression of CsLAC17 significantly increased the lignin content in transgenic Arabidopsis , enhancing their resistance to gray blight and decreasing stem tenderness. In addition, we found that CsLAC17 was negatively regulated by the upstream CsmiR397a by 5'-RLM-RACE, dual-luciferase assay, and transient expression in young tea shoots. Interestingly, the expression of CsmiR397a was inhibited during tenderness reduction and gray blight infection of young tea shoots. Overexpression of CsmiR397a reduced lignin accumulation, resulting in decreased resistance to gray blight and increased stem tenderness in transgenic Arabidopsis . Furthermore, the transient overexpression of CsmiR397a and CsLAC17 in tea leaves directly confirms the function of the CsmiR397a - CsLAC17 module in lignin biosynthesis and its effect on disease resistance. These results suggest that the CsmiR397a-CsLAC17 module is involved in balancing tenderness and gray blight resistance in young tea shoots by regulating lignin biosynthesis., Competing Interests: The authors declare that they have no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Objective . In previous studies, the factors affecting the accuracy of imaging photoplethysmography (iPPG) heart rate (HR) measurement have been focused on the light intensity, facial reflection angle, and motion artifacts. However, the factor of specularly reflected light has not been studied in detail. We explored the effect of specularly reflected light on the accuracy of HR estimation and proposed an estimation method for the direction of specularly radiated light. Approach . To study the HR measurement accuracy influenced by specularly reflected light, we control the component of specularly reflected light by controlling its angle. A total of 100 videos from four different reflected light angles were collected, and 25 subjects participated in the dataset collection. We extracted angles and illuminations for 71 facial regions, fitting sample points through interpolation, and selecting the angle corresponding to the maximum weight in the fitted curve as the estimated reflected angle. Main results . The experimental results show that higher specularly reflected light compromises HR estimation accuracy under the same value of light intensity. Notably, at a 60° angle, the HR accuracy (ACC) increased by 0.7%, while the signal-to-noise ratio and Pearson correlation coefficient increased by 0.8 dB and 0.035, respectively, compared to 0°. The overall root mean squared error, standard deviation, and mean error of our proposed reflected light angle estimation method on the illumination multi-angle incidence (IMAI) dataset are 1.173°, 0.978°, and 0.773°. The average Pearson value is 0.8 in the PURE rotation dataset. In addition, the average ACC of HR measurements in the PURE dataset is improved by 1.73% in our method compared to the state-of-the-art traditional methods. Significance . Our method has great potential for clinical applications, especially in bright light environments such as during surgery, to improve accuracy and monitor blood volume changes in blood vessels., (© 2024 Institute of Physics and Engineering in Medicine.)

Circular dichroism (CD) spectrometry is a rapid technique for detecting protein secondary structure, particularly helicity. DMSO is used to ensure optimal solubility of peptides/peptidomimetics; however, its background absorbance hinders effective CD analysis. Here, we present a protocol for reconstituting peptides/peptidomimetics from DMSO to aqueous buffers for CD analyses. We describe steps for identifying chemicals that induce DMSO evaporation, extracting peptides/peptidomimetics from DMSO, and CD spectrometer setup and analysis. We then detail procedures for secondary structure analyses of reconstituted peptides/peptidomimetics. For complete details on the use and execution of this protocol, please refer to Gao et al. (2023). 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Poly (ADP-ribose) polymerase-1 (PARP-1) activity significantly increases during cerebral ischemia/reperfusion. PARP-1 is an NAD + -consumption enzyme. PARP-1 hyperactivity causes intracellular NAD + deficiency and bioenergetic collapse, contributing to neuronal death. Besides, the powerful trigger of PARP-1 causes the catalyzation of poly (ADP-ribosyl)ation (PARylation), a posttranslational modification of proteins. Here, we found that PARP-1 was activated in the ischemic brain tissue during middle-cerebral-artery occlusion and reperfusion (MCAO/R) for 24 h, and PAR accumulated in the neurons in mice. Using immunoprecipitation, Western blotting, liquid chromatography-mass spectrometry, and 3D-modeling analysis, we revealed that the activation of PARP-1 caused PARylation of hexokinase-1 and lactate dehydrogenase-B, which, therefore, caused the inhibition of these enzyme activities and the resulting cell energy metabolism collapse. PARP-1 inhibition significantly reversed the activity of hexokinase and lactate dehydrogenase, decreased infarct volume, and improved neuronal deficiency. PARP-1 inhibitor combined with pyruvate further alleviated MCAO/R-induced ischemic brain injury in mice. As such, we conclude that PARP-1 inhibitor alleviates neuronal death partly by inhibiting the PARylation of metabolic-related enzymes and reversing metabolism reprogramming during cerebral ischemia/reperfusion injury in mice. PARP-1 inhibitor combined with pyruvate might be a promising therapeutic approach against brain ischemia/reperfusion injury., 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.)

Objective: The study attempted to explore how allicin reduces oxidative stress levels by promoting SHP2 expression to inhibit p-PERK in I/R mice., Methods: The GEO database and RNA sequencing were used to predict downstream gene. TTC staining was used to visualize the myocardial infarction area. Masson staining was used to assess the level of fibrosis. IF was used to examine the expression of SHP2, CTGF, ROS. RT-PCR analysis was used to quantify the expression of SHP2 mRNA. Western blot was used to detect the protein expression levels of SHP2, p-PERK, MFN1, NLRP3, NOX2, and NOX3., Results: GEO and transcriptomic data revealed low expression of SHP2 in the heart tissues I/R mice. In the I/R mouse model, TTC staining result showed that allicin can reduce the area of myocardial infarction; Masson staining results indicated that allicin can reduce fibrosis; Macrophage transcriptome sequencing found SHP2 is a target gene of allicin; Immunofluorescence showed allicin can increase SHP2; qPCR results showed allicin can raise SHP2 mRNA level; Immunofluorescence indicated that allicin can inhibit ROS in myocardial infarction tissue, but the specific SHP2-KD eliminates changes in ROS. Western blot analysis demonstrated allicin can increase SHP2 protein and reduce the expression of p-PERK, MFN1, NLRP3, NOX2, and NOX3; SHP2-KD eliminates the expression differences in p-PERK, MFN1, NLRP3, NOX2, and NOX3., Conclusions: Allicin can modulate p-PERK activation by enhancing the expression of SHP2, thereby inhibiting myocardial ischemia-reperfusion-induced oxidative stress in mice.

This study aims to explore the specific mechanism by which miR-155 regulates SHP2 expression in mouse ischemia-reperfusion (I/R) induced necroptosis. Various methods including cardiac ultrasound, TTC staining, Masson staining, TUNEL staining, and Western blotting were used to examine changes in the morphology and function of the rat left ventricle, myocardial fibrosis, as well as the expression of proteins related to tissue and cardiomyocyte necroptosis pathways. In vivo results showed that knockdown (KD) of miR-155 significantly improved cardiac ultrasound parameters (EF, FS, LVAW;d, and LVAW;s), reduced the myocardial infarction area, myocardial fibrosis, and cell apoptosis in I/R mice, upregulated cardiac SHP2 protein expression, and other proteins including p-ERK1/2, NLRP3, GSDMD, caspase-3, caspase-4, and caspase-11 were also significantly decreased. In vitro experiments showed that compared with the SHP2 WT miR-155 KD group, SHP2 protein expression was significantly increased in the SHP2 WT miR-155 KD group, while the expression of other proteins was significantly reduced, consistent with in vivo results. MiR-155 can regulate ERK1/2 and NLRP3 through SHP2. After adding the ERK1/2 inhibitor U0126 to cardiomyocytes from SHP2 KO mice, it was found that the expression of proteins other than SHP2 significantly decreased compared to SHP2 KO cells without the inhibitor. In summary, low expression of miR-155 promoted the expression of SHP2 and improved mouse I/R-induced necroptosis by inhibiting the activation of the ERK1/2 pathway.

Tumor immune escape caused by low levels of tumor immunogenicity and immune checkpoint-dependent suppression limits the immunotherapeutic effect. Herein, a "two-way regulation" epigenetic therapeutic strategy is proposed using a novel nano-regulator that inhibits tumor immune escape by upregulating expression of tumor-associated antigens (TAAs) to improve immunogenicity and downregulating programmed cell death 1 ligand 1 (PD-L1) expression to block programmed death-1 (PD-1)/PD-L1. To engineer the nano-regulator, the DNA methyltransferase (DNMT) inhibitor zebularine (Zeb) and the bromodomain-containing protein 4 (BRD4) inhibitor JQ1 are co-loaded into the cationic liposomes with condensing the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine (CpG) via electrostatic interactions to obtain G-J/ZL. Then, asparagine-glycine-arginine (NGR) modified material carboxymethyl-chitosan (CMCS) is coated on the surface of G-J/ZL to construct CG-J/ZL. CG-J/ZL is shown to target tumor tissue and disassemble under the acidic tumor microenvironment (TME). Zeb upregulated TAAs expression to improve the immunogenicity; JQ1 inhibited PD-L1 expression to block immune checkpoint; CpG promote dendritic cell (DC) maturation and reactivated the ability of tumour-associated macrophages (TAM) to kill tumor cells. Taken together, these results demonstrate that the nano-regulator CG-J/ZL can upregulate TAAs expression to enhance T-cell infiltration and downregulate PD-L1 expression to improve the recognition of tumor cells by T-cells, representing a promising strategy to improve antitumor immune response., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Soft magnetic materials with flake geometry can provide shape anisotropy for breaking the Snoek limit, which is promising for achieving high-frequency ferromagnetic resonances and microwave absorption properties. Here, two-dimensional (2D) Fe 3 C microflakes with crystal orientation are obtained by solid-state phase transformation assisted by electrochemical dealloying. The shape anisotropy can be further regulated by manipulating the thickness of 2D Fe 3 C microflakes under different isothermally quenching temperatures. Thus, the resonant frequency is adjusted effectively from 9.47 and 11.56 GHz under isothermal quenching from 700 °C to 550 °C. The imaginary part of the complex permeability can reach 0.9 at 11.56 GHz, and the minimum reflection loss (RL min ) is -52.09 dB (15.85 GHz, 2.90 mm) with an effective absorption bandwidth (EAB ≤-10 dB ) of 2.55 GHz. This study provides insight into the preparation of high-frequency magnetic loss materials for obtaining high-performance microwave absorbers and achieves the preparation of functional materials from traditional structural materials., (© 2024. The Author(s).)

In trees, injuries resulting from subfreezing temperatures can cause damage to the cellular biofilm system, metabolic functions, and fibrous reticulum, and even cell death. Investigating the occurrence of freezing damage and its contributing factors could help understand the mechanisms underlying freezing injury and prevent the subsequent damage in trees. To achieve this, a laboratory experiment was conducted using cut wood samples from Korean pine ( Pinus koraiensis Siebold & Zucc) and Simon poplar ( Populus simonii Carr.), and the effects of environmental freezing factors, including freezing temperatures, freezing duration, and cooling rate, on the temperature at which freezing injuries occur were examined using the electrical impedance spectroscopy (EIS) method. The semi-lethal temperature (LT50), as an indicator of freezing injury in wood tissue, was theoretically deduced based on the measured extracellular resistance ( r e ) using EIS. The contributory factors to changes in LT50 were determined and their relationship was established. The results revealed that all freezing factors exhibited significant effects on electrical impedance characteristics ( r e , r i , and τ), significantly influencing the LT50 of the wood. Random forest (RF) and support vector machine (SVM) models were used to assess the contribution of the freezing factors and moisture content (MC). Among the factors examined, freezing duration had the greatest impact on LT50, followed by the MC, whereas the contribution of the cooling rate was minimal. The model accuracies were 0.89 and 0.86 for Korean pine and Simon poplar, respectively. The findings of our study illustrate that the occurrence of freezing injury in trees is primarily influenced by the duration of freezing at specific subzero temperatures. Slow cooling combined with prolonged freezing at low subzero temperatures leads to earlier and more severe freezing damage., 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 © 2024 Song, Gao, Ai and Gao.)

Purification of ethylene (C 2 H 4 ) as the most extensive and output chemical, from complex multi-components is of great significance but highly challenging. Herein we demonstrate that precise pore structure tuning by controlling the network hydrogen bonds in two highly-related porous coordination networks can shift the efficient C 2 H 4 separation function from C 2 H 2 /C 2 H 4 /C 2 H 6 ternary mixture to CO 2 /C 2 H 2 /C 2 H 4 /C 2 H 6 quaternary mixture system. Single-crystal X-ray diffraction revealed that the different amino groups on the triazolate ligands resulted in the change of the hydrogen bonding in the host network, which led to changes in the pore shape and pore chemistry. Gas adsorption isotherms, adsorption kinetics and gas-loaded crystal structure analysis indicated that the coordination network Zn-fa-atz (2) weakened the affinity for three C2 hydrocarbons synchronously including C 2 H 4 but enhanced the CO 2 adsorption due to the optimized CO 2 -host interaction and the faster CO 2 diffusion, leading to effective C 2 H 4 production from the CO 2 /C 2 H 2 /C 2 H 4 /C 2 H 6 mixture in one step based on the experimental and simulated breakthrough data. Moreover, it can be shaped into spherical pellets with maintained porosity and separation performance., (© 2024. The Author(s).)

Objectives: To assess the efficacy and safety of direct oral anticoagulants (DOACs) in comparison to standard-of-care (SOC) anticoagulants in the management and prophylaxis of thromboembolic events in pediatric populations., Methods: A comprehensive search of electronic databases was conducted to identify relevant studies published between January 1, 2015, and December 18, 2022. A meta-analysis was undertaken to evaluate the effect of DOACs on clinically significant endpoints, employing trial-level data with harmonized endpoint definitions. The primary outcome was venous thromboembolism (VTE). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The study was registered with INPLASY (2022120065)., Results: Three studies encompassing 934 subjects were included. The incidence of VTE was reduced in patients administered DOACs compared to those on SOC anticoagulants (OR 0.41 [95% CI 0.19-0.93], I² = 0%, P = 0.03). No significant differences were observed between the DOAC and SOC groups in all-cause mortality (OR 0.50 [95% CI 0.07-3.59], I² = 0%, P = 0.35) or serious adverse events (OR 0.75 [95% CI 0.50-1.12], I² = 0%, P = 0.16). The risk of major bleeding (OR 0.50 [95% CI 0.13-1.87], I² = 44%, P = 0.30) and clinically relevant non-major bleeding (OR 1.23 [95% CI 0.50-3.00], I² = 0%, P = 0.65) exhibited no significant differences between the groups., Conclusions: DOACs are associated with a reduced risk of VTE in pediatric patients without increasing the risk of bleeding, all-cause mortality, or serious adverse events when compared to SOC anticoagulants. DOACs may be an alternative for the treatment and prevention of thromboembolic events in the pediatrics., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Developing a multifunctional hydrogel wound dressing with good injectability, self-healing, tissue adhesion, biocompatibility, and fast skin wound healing efficiency remains challenging. In this work, an injectable adhesive dopamine-functionalized oxidized hyaluronic acid/carboxymethyl chitosan/collagen (AHADA/CCS/Col) hydrogel was constructed. The Schiff dynamic bond between AHADA and CCS, the N-Ag-N bond between CCS and Ag ions, and the S-Ag-S dynamic bond between sulfhydryl-modified collagen (ColSH) and Ag ions allowed the hydrogel to be both injectable and self-healing. Moreover, the aldehyde groups and catechol groups presented in the hydrogel could generate force with several groups on the tissue interface; therefore, the hydrogel also had good tissue adhesion. In vitro experiments proved that this hydrogel exhibited good biocompatibility and could promote cell proliferation. Additionally, curcumin (Cur)-loaded gelatin nanoparticles (Cur@Gel NPs) were prepared, which could respond to matrix metalloproteinases (MMPs) and controllably release Cur to hasten wound healing efficiency. Animal experiment results showed that this AHADA/CCS/Col hydrogel loaded with Cur@Gel NPs promoted wound repairing better, indicating its potential as a wound dressing.

Competing Interests: Declaration of interests We declare no competing interests.

Haze seriously affects the visual quality of road inspection images and contaminates the discrimination of key road objects, which thus hinders the execution of road inspection work. The basic assumptions of the classical dark-channel prior are not suitable for road images containing light-colored lane lines and vehicles, while typical deep dehazing networks lack physical model interpretability, and they focus on global dehazing effects, neglecting the preservation of object features. For this reason, this paper proposes a Dark-Channel Soft-Constrained and Object-Perception-Enhanced Deep Dehazing Network (DCSC-OPE-Net) for the information recovery of road inspection images. The network is divided into two modules: a dark-channel soft-constrained dehazing module and a near-view object-perception-enhanced module. Unlike the traditional dark-channel algorithms that impose strong constraints on dark pixels, a dark-channel soft-constrained loss function is constructed to ensure that the features of light-colored vehicles and lane lines are effectively maintained. To avoid resolution loss due to patch-based dark-channel processing for image dehazing, a resolution enhancement module is used to strengthen the contrast of the dehazed image. To autonomously perceive and enhance key road features to support road inspection, edge enhancement loss combined with a transmission map is embedded into the network to autonomously discover near-view objects and enhance their key features. The experiments utilize public datasets and real road inspection datasets to validate the performance of the proposed DCSC-OPE-Net compared with typical networks using dehazing evaluation metrics and road object recognition metrics. The experimental results demonstrate that the proposed DCSC-OPE-Net can obtain the best dehazing performance, with an NIQE score of 4.5 and a BRISQUE score of 18.67, and obtain the best road object recognition results (i.e., 83.67%) among the comparison methods.

Cation-disordered Rocksalt oxides (DRXs) are a promising new class of cathode materials for Li-ion batteries due to their natural abundance, low cost and great electrochemical performance. High entropy strategy in Mn-based DRXs appears to be an effective strategy for improving the rate capability, but it suffers from challenges including capacity degradation. The present paper reports a new group of high entropy DRXs (HE DRX) based on Ni 2+ -Nb 5+ pair; the structural and chemical evolution upon cycling of DRXs with an increasing transition metal (TM) species are systematically investigated. An explanation is proposed for how the crystal field stability energy determines that HE DRX could exist in single Rocksalt solid solution structures. We further reveal that the charge compensation mechanism in HE DRX is the result of various TM synergistic effect. More importantly, through various in situ and ex situ techniques and theoretical calculation, the effective integration of more TM cation species within the HE DRX framework promotes better Li + diffusion and improves lattice oxygen stability, consequently increasing capacity upon cycling., (© 2023 Wiley-VCH GmbH.)

Background: With the publication of a large number of clinical studies on antiplatelet therapy in recent years, it is still controversial which antiplatelet monotherapy should be continued after a period of dual antiplatelet therapy (DAPT) in the post percutaneous coronary intervention (post-PCI) population. We conducted a meta-analysis to investigate the efficacy and safety of P2Y 12 inhibitors versus aspirin in the post-PCI population after completing DAPT., Methods: We searched studies in electronic databases from January 1, 2015 to November 20, 2022. We conducted a meta-analysis to estimate the effect of P2Y 12 inhibitor monotherapy on clinical end-points in post-PCI patients after a period of DAPT, using trial-level data with consistent end-point definitions. The primary outcome was major adverse cardiovascular events (MACE). Odd ratio (OR) was pooled with 95% confidence interval (CI) for dichotomous data. This study is registered with INPLASY 2022120011., Results: We included five studies that included 24,460 patients. The patients who received a P2Y 12 inhibitor showed a lower risk of MACE than patients who received aspirin (OR 0.70 [95% CI 0.60-0.80], I 2 = 0%, p < 0.00001) monotherapy. Subgroup analysis of MACE based on patient characteristics showed consistent results with the main analysis. The risk of major bleeding was similar in patients who received a P2Y 12 inhibitor and those who received aspirin (OR 0.86 [95% CI 0.53-1.39], I 2 = 57%, p = 0.54). The risk of major bleeding was borderline increased in patients who received ticagrelor versus aspirin (OR 1.81 [95% CI 0.99-3.31], p = 0.05)., Conclusions: In the post-PCI population, P2Y 12 inhibitor monotherapy may be superior to aspirin for MACE, repeat revascularization, and stroke without increasing the risk of major bleeding., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Chemoimmunotherapy has been approved as standard treatment for triple-negative breast cancer (TNBC), but the clinical outcomes remain unsatisfied. Abnormal epigenetic regulation is associated with acquired drug resistance and T cell exhaustion, which is a critical factor for the poor response to chemoimmunotherapy in TNBC. Herein, macrophage-camouflaged nanoinducers co-loaded with paclitaxel (PTX) and decitabine (DAC) (P/D-mMSNs) were prepared in combination with PD-1 blockade therapy, hoping to improve the efficacy of chemoimmunotherapy through the demethylation of tumor tissue. Camouflage of macrophage vesicle confers P/D-mMSNs with tumor-homing properties. First, DAC can achieve demethylation of tumor tissue and enhance the sensitivity of tumor cells to PTX. Subsequently, PTX induces immunogenic death of tumor cells, promotes phagocytosis of dead cells by dendritic cells, and recruits cytotoxic T cells to infiltrate tumors. Finally, DAC reverses T cell depletion and facilitates immune checkpoint blockade therapy. P/D-mMSNs may be a promising candidate for future drug delivery design and cancer combination therapy in TNBC., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Objective: This study aims to evaluate the efficacy of photodynamic therapy (PDT) in the treatment of oral leukoplakia and explore the subgroup factors that may influence its effectiveness., Methods: A systematic search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science databases to identify relevant studies. Meta-analysis was performed using Stata15.0 software. Cochran's Q test and I 2 statistics were used to evaluate heterogeneity, egger's test was used to evaluate publication bias., Results: The analysis of 17 studies included in this study suggests that PDT may be effective in achieving complete response (CR) [ES = 0.50, 95%CI: (0.33,0.66)], partial response (PR) [ES = 0.42, 95%CI: (0.27,0.56)], no response (NR) [ES = 0.19, 95%CI: (0.11,0.27)]in patients with oral leukoplakia. The recurrence rate was also evaluated [ES = 0.13, 95%CI: (0.08,0.18)]. Subgroup analysis showed that various factors such as light source, wavelength, medium, duration of application, clinical and pathological diagnosis classification influenced efficacy of PDT. The lesion areas of the leukoplakia after treatment were reduced by 1.97cm 2 compared with those before treatment., Conclusion: Our findings show that PDT is a viable treatment for oral leukoplakia. However, the effectiveness of the therapy may depend on several factors, as suggested by our subgroup analyses. (Registration no. CRD42023399848 in Prospero, 26/02/2023)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Integrins are ubiquitously expressed cell-adhesion proteins. Activation of integrins is triggered by talin through an inside-out signaling pathway, which can be driven by RAP1-interacting adaptor molecule (RIAM) through its interaction with talin at two distinct sites. A helical talin-binding segment (TBS) in RIAM interacts with both sites in talin, leading to integrin activation. The bispecificity inspires a "double-hit" strategy for inhibiting talin-induced integrin activation. We designed an experimental peptidomimetic inhibitor, S-TBS, derived from TBS and containing a molecular staple, which leads to stronger binding to talin and inhibition of talin:integrin interaction. The crystallographic study validates that S-TBS binds to the talin rod through the same interface as TBS. Moreover, the helical S-TBS exhibits excellent cell permeability and effectively suppresses integrin activation in cells in a talin-dependent manner. Our results shed light on a new class of integrin inhibitors and a novel approach to design multi-specific peptidomimetic inhibitors., Competing Interests: Declaration of interests J.W. declares a pending patent application PCT/US22/14238 filed on January 28, 2022., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Diabetic foot infection (DFI) is a common complication in diabetes patients, with foot infections being the leading cause of amputations. Staphylococcus aureus is frequently found in diabetic foot infections, of which methicillin-resistant Staphylococcus aureus (MRSA) has become a major clinical and epidemiological challenge. Since MRSA strains are resistant to most β-lactam antibiotics, and also partially resistant to other antibiotics, treatment is difficult and costly. The emergence of drug-resistant bacteria often arises from overuse or misuse of antibiotics. Clinically, canagliflozin is commonly used for the treatment of type 2 diabetes. On this basis, we investigated the antibacterial activity and mechanism of canagliflozin against MRSA, with the aim to discover novel functions of canagliflozin and provide new insights for the treatment of MRSA. Using the microbroth dilution method to determine the half maximal inhibitory concentration of drugs, we found that canagliflozin not only can inhibit the growth of methicillin-sensitive Staphylococcus aureus (MSSA) but also exhibits antibacterial activity against MRSA. The IC50 values, at approximately 56.01 μM and 57.60 μM, were almost the same. At 12 h, canagliflozin showed a significant antibacterial effect against MRSA at and above 30 μM. In addition, its combined use with penicillin achieved better antibacterial effects, which were increased by about three times. Additive antibacterial activity (FICI = 0.69) was found between penicillin and canagliflozin, which was better than that of doxycycline and canagliflozin (FICI = 0.95). Canagliflozin also affected bacterial metabolic markers, such as glucose, ATP, and lactic acid. The results of crystal violet staining indicate that canagliflozin disrupted the formation of bacterial biofilm. Our electron microscopy results showed that canagliflozin distorted the bacterial cell wall. The results of RT-PCR suggest that canagliflozin down-regulated the expressions of biofilm-related gene (clfA, cna, agrC, mgrA, hld) and methicillin-resistance gene (mecA), which was related to MRSA. Molecular docking also indicated that canagliflozin affected some interesting targets of MRSA, such as the sarA, crtM and fnbA proteins. In conclusion, canagliflozin exhibits antibacterial activity against MRSA by affecting bacterial metabolism, inhibiting its biofilm formation, distorting the bacterial cell wall, and altering the gene expression of biofilm formation and its virulence. Our study reveals the antibacterial activity of canagliflozin against MRSA, providing a new reference for treating diabetic foot infections.

The cancer-associated fibroblast (CAF) barrier in pancreatic ductal adenocarcinoma (PDAC) greatly restricts clinical outcomes. Major obstacles to PDAC treatment include restricted immune cell infiltration and drug penetration and the immunosuppressive microenvironment. Here, we reported a "shooting fish in a barrel" strategy by preparing a lipid-polymer hybrid drug delivery system (PI/JGC/L-A) that could overcome the CAF barrier by turning it into a "barrel" with antitumor drug depot properties to alleviate the immunosuppressive microenvironment and increase immune cell infiltration. PI/JGC/L-A is composed of a pIL-12-loaded polymeric core (PI) and a JQ1 and gemcitabine elaidate coloaded liposomal shell (JGC/L-A) that has the ability to stimulate exosome secretion. By normalizing the CAF barrier to create a CAF "barrel" with JQ1, stimulating the secretion of gemcitabine-loaded exosomes from the CAF "barrel" to the deep tumor site, and leveraging the CAF "barrel" to secrete IL-12, PI/JGC/L-A realized effective drug delivery to the deep tumor site, activated antitumor immunity at the tumor site, and produced significant antitumor effects. In summary, our strategy of transforming the CAF barrier into antitumor drug depots represents a promising strategy against PDAC and might benefit the treatment of any tumors facing a drug delivery barrier.

Ubiquitin-specific proteases (USPs) 28 is overexpressed in multiple types of cancers. The development of potent USP28 inhibitors is still in primitive stage. We previously reported our discovery of Vismodegib as a USP28 inhibitor by screening a commercially available drug library. Herein, we report our efforts to solve the cocrystal structure of Vismodegib bound to USP28 for the first time and subsequent structure-based optimization leading to a series of Vismodegib derivatives as potent USP28 inhibitors. Based on the cocrystal structure, elaborative SARs exploration was carried out to afford much more potent USP28 inhibitors than Vismodegib. The representative compounds 9l, 9o and 9p bearing high potency on USP28 showed high selectivity over USP2, USP7, USP8, USP9x, UCHL3 and UCHL5. The detailed cellular assay suggested that compounds 9l, 9o and 9p could cause cytotoxicity in both human colorectal cancer and lung squamous carcinoma cells and significantly enhance the sensitivity of colorectal cancer cells to Regorafenib. Further immunoblotting analysis indicated that compounds 9l, 9o and 9p could dose-dependently down-regulate the cellular level of c-Myc through ubiquitin-proteasome system and anti-cancer effects could mainly be attributed to their inhibition on USP28 but not involving the Hedgehog-Smoothened pathway. Thus, our work provided a series of novel and potent USP28 inhibitors derived from Vismodegib and may contribute to the development of USP28 inhibitors., 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 Masson SAS. All rights reserved.)

Cytotoxic T lymphocytes (CTLs) are central effector cells in antitumor immunotherapy. However, the complexity of immunosuppressive factors in the immune system contributes to the low response rates of current CTL-based immunotherapies. Here, we propose a novel holistic strategy including a priming response, promoting activity, and relieving suppression of CTLs, aiming to strengthen the effect of personalized postoperative autologous nanovaccines. The nanovaccine (C/G-HL-Man) fused the autologous tumor cell membrane with dual adjuvants (CpG and cGAMP), and could effectively accumulate in lymph nodes and promote antigen cross presentation by dendritic cells to prime a sufficient specific-CTL response. The PPAR-α agonist fenofibrate was used to regulate T-cell metabolic reprogramming to promote antigen-specific CTLs activity in the harsh metabolic tumor microenvironment. Finally, the PD-1 antibody was used to relieve the suppression of specific-CTLs in the immunosuppressive tumor microenvironment. In vivo, the C/G-HL-Man exhibited strong antitumor effect in the B16F10 murine tumor prevention model and the B16F10 postoperative recurrence model. In particular, combination therapy with nanovaccines, fenofibrate, and PD-1 antibody effectively inhibited the progression of recurrent melanoma and prolonged the survival time. Our work highlights the critical role of the T-cell metabolic reprogramming and PD-1 blocking in autologous nanovaccines, offering a novel strategy for strengthening the function of CTLs., 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.)

We present a multi-material three-dimensional-printed snakeskin with orthotropic friction anisotropy, which permits undulatory slithering of a soft snake robot on rough surfaces. Such a snakeskin is composed of a soft skin base and embedded rigid scales attached to the robot's ventral surface. The bioinspired designs of scale shapes and arrangements lead effectively to various types of anisotropic friction, and provide means of switching robot's locomotion direction to be either the same as or opposite to the propagation direction of the traveling-wave undulation. Furthermore, steering of locomotion can be achieved by applying additional pressure bias in one air path to break symmetry of body deformation. We also successfully demonstrate the snake robot's mobility on various outdoor rough substrates, including concrete surfaces and a grass lawn, as well as pipes of different dimensions and materials, for potential field applications.

An Al-15 Al 2 O 3 alloy was added into Al-12Si melt to investigate the nano-treating effect of Al 2 O 3 nanoparticles on eutectic Si crystals. It was found that Al 2 O 3 clusters may be partly swallowed by eutectic Si or distribute surrounding them. As a result, the flake-like eutectic Si in Al-12Si alloy can transform to granular or worm-like morphologies, attributing to the influence of Al 2 O 3 nanoparticles on the growth behavior of eutectic Si crystals. The orientation relationship between Si and Al 2 O 3 was identified, and the possible modifying mechanisms were discussed., 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.)