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Aurantii Fructus Immaturus (AFI) was structurally divided into two parts named "peel" and "pulp". The exocarp and mesocarp of materials named "peel". The endocarp separated into multiple compartments and the cystic hair attached to it named "pulp". In order to explore the distribution and content of constituents in AFI, an efficient method to explore the distribution of constituents was developed based on matrix assisted laser desorption/ionization fourier transform ion cyclotron resonance mass spectrometry imaging (MALDI-FTICR-MSI). After simple processing, thirty-two constituents with distinct localization in the mass range of 101-1200 Da were identified by MALDI-FTICR-MSI. In addition, the identified four flavnoids (poncirin, sinensetin, 3,5,6,7,8,3',4'-heptemthoxyflavone, and tangeritin) were analyzed for differences between using LC-MS. Quantitative analysis results supported the quantitative results from MALDI-FT-ICR-MSI. The results implied that different parts had different constituents in AFI, and demonstrated MALDI-MSI have high potential in the direct analysis of constituents., Competing Interests: Declaration of competing interest The authors do not have any conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Given the escalating incidence of bacterial diseases and the challenge posed by pathogenic bacterial resistance, it is imperative to identify appropriate methodologies for conducting proteomic investigations on bacteria, and thereby promoting the target-based drug/pesticide discovery. Interestingly, a novel technology termed "activity-based protein profiling" (ABPP) has been developed to identify the target proteins of active molecules. However, few studies have summarized advancements in ABPP for identifying the target proteins in antibacterial-active compounds. In order to accelerate the discovery and development of new drug/agrochemical discovery, we provide a concise overview of ABPP and its recent applications in antibacterial agent discovery. Diversiform cases were cited to demonstrate the potential of ABPP for target identification though highlighting the design strategies and summarizing the reported target protein of antibacterial compounds. Overall, this review is an excellent reference for probe design towards antibacterial compounds, and offers a new perspective of ABPP in bactericide development., 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 Inc. All rights reserved.)

Introduction: To examine the influence of adjuvant chemoradiation therapy (CRT) on survival, stratified by varying numbers and level involved of metastatic lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC)., Methods: Patients who underwent surgery for metastatic, negative margin HNSCC without extranodal extension were retrospectively enrolled and divided into two groups based on adjuvant therapy received: radiotherapy (RT) and CRT. The impact of RT versus CRT, stratified by the number of positive lymph nodes and the level involved, on Disease-Free Survival (DFS) and Overall Survival (OS) was analyzed., Results: Following propensity score matching, a total of 580 patients were included. The burden and level of lymph node metastasis were independent predictors of poorer survival. Among patients with no more than two positive lymph nodes or involvement of levels I-III, the addition of chemotherapy to RT did not demonstrate a significant improvement in prognosis. However, in patients with three or more positive lymph nodes, CRT showed improved DFS and OS compared to RT. In patients with involvement of levels IV-V, the addition of chemotherapy to RT resulted in a significant 24 % reduction in the risk of recurrence and a 20 % decrease in the risk of death., Conclusion: Incorporation of adjuvant chemoradiation can lead to a favorable prognosis in patients with metastatic HNSCC. This impact was notable in cases where there were three or more positive lymph nodes or involvement of levels IV-V., 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, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Colostrum and milk offer a complete diet and vital immune protection for newborn mammals with developing immune systems. High immunoglobulin levels in colostrum serve as the primary antibody source for newborn piglets and calves. Subsequent milk feeding support continued local antibody protection against enteric pathogens, as well as maturation of the developing immune system and provide nutrients for newborn growth. Mammals have evolved hormonal strategies that modulate the levels of immunoglobulins in colostrum and milk to facilitate effective lactational immunity. In addition, hormones regulate the gut-mammary gland-secretory immunoglobulin A (sIgA) axis in pregnant mammals, controlling the levels of sIgA in milk, which serves as the primary source of IgA for piglets and helps them resist pathogens such as PEDV and TGEV. In the present study, we review the existing studies on the interactions between hormones and the gut-mammary-sIgA axis/lactogenic immunity in mammals and explore the potential mechanisms of hormonal regulation that have not been studied in detail, to draw attention to the role of hormones in influencing the immune response of pregnant and lactating mammals and their offspring, and highlight the effect of hormones in regulating sIgA-mediated anti-infection processes in colostrum and milk. Discussion of the relationship between hormones and lactogenic immunity may lead to a better way of improving lactogenic immunity by determining a better injection time and developing new vaccines., 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. Published by Elsevier Inc.)

Objectives: The prevalence of gestational diabetes mellitus (GDM) has been increasing globally over recent decades; however, underlying reasons for the increase remain unclear. We analyzed trends in GDM rates and evaluated risk factors associated with the observed trends in Ontario, Canada., Methods: We conducted a retrospective population-based cohort study using the Better Outcomes Registry and Network Ontario, linked with the Canadian Institute for Health Information Discharge Abstract Database. All pregnant individuals who had a singleton hospital delivery from 1 April 2012 to 31 March 2020 were included. We calculated rates and 95% CIs for GDM by year of delivery and contrasted fiscal year 2019/20 with 2012/13. Temporal trends in GDM were quantified using crude and adjusted risk ratios by modified Poisson regression. We further quantified the temporal increase attributable to changes in maternal characteristics by decomposition analysis., Results: Among 1 044 258 pregnant individuals, 82 896 (7.9%) were diagnosed with GDM over the 8 years. GDM rate rose from 6.1 to 10.4 per 100 deliveries between fiscal years 2012/13 and 2019/20. The risk of GDM in 2019/20 was 1.53 times (95% CI 1.50-1.56) higher compared with 2012/13. 27% of the increase in GDM was due to changes in maternal age, 8 BMI, and Asian ethnicity., Conclusions: The GDM rate has been consistently increasing in Ontario, Canada. The contribution of increasing maternal age, pre-pregnancy obesity, and Asian ethnicity to the recent increase in GDM is notable. Further investigation is required to better understand the contributors to increasing GDM., (Copyright © 2024 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: Low-grade glioma (LGG) has an extremely poor prognosis, and the mechanism leading to malignant development has not been determined. The aim of our study was to clarify the function and mechanism of anoikis and TIMP1 in the malignant progression of LGG., Methods: We screened 7 anoikis-related genes from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to construct a prognostic-predicting model. The study assessed the clinical prognosis, pathological characteristics, and immune cell infiltration in both high- and low-risk groups. Additionally, the potential modulatory effects of TIMP1 on proliferation, migration, and anoikis in LGG were investigated both in vivo and in vitro., Results: In this study, we identified seven critical genes, namely, PTGS2, CCND1, TIMP1, PDK4, LGALS3, CDKN1A, and CDKN2A. Kaplan‒Meier (K‒M) curves demonstrated a significant correlation between clinical features and overall survival (OS), and single-cell analysis and mutation examination emphasized the heterogeneity and pivotal role of hub gene expression imbalances in LGG development. Immune cell infiltration and microenvironment analysis further elucidated the relationships between key genes and immune cells. In addition, TIMP1 promoted the malignant progression of LGG in both in vitro and in vivo models., Conclusions: This study confirmed that TIMP1 promoted the malignant progression of LGG by inhibiting anoikis, providing insights into LGG pathogenesis and potential therapeutic targets., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Brain contusion is a prevalent traumatic brain injury (TBI) in low-age children, bearing the potential for coma and fatality. Hence, it is imperative to undertake comprehensive research in this field., Methods: This study employed 4-week-old piglets as surrogates for children and introduced self-designed devices for both free-fall drop impact tests and drop-hammer impact tests. The study explored the characteristics of brain contusion and dynamic responses of brain under these distinct testing conditions., Results: Brain contusions induced by free-fall and drop-hammer conditions both were categorized as the coup injury, except that slight difference in the contusion location was observed, with contusion occurring mainly in the surrounding regions beneath the impact location under free-fall condition and the region just right beneath the impact location under drop-hammer condition. Analysis of impact force and intracranial pressure (ICP) curves indicated similar trends in impact forces under both conditions, yet different trends in ICPs. Further examination of the peak impact forces and ICPs elucidated that, with increasing impact energy, the former followed a combined power and first-order polynomial function, while the latter adhered to a power function. The brain contusion was induced at the height (energy) of 2 m (17.2 J), but not at the heights of 0.4, 0.7, 1, 1.35 and 1.7 m, when the vertex of the piglet head collided with a rigid plate. In the case of a cylindrical rigid hammer (cross-sectional area constituting 40 % of the parietal bone) striking the head, the brain contusion was observed under the energy of 21.9 J, but not under energies of 8.1 J, 12.7 J and 20.3 J. Notably, the incidence of brain contusion was more pronounced under the free-fall condition., Conclusions: These findings not only facilitate a comprehensive understanding of brain contusion dynamics in pediatric TBIs, but also contribute to the validation of theories and finite element models for piglet heads, which are commonly employed as surrogates for children., 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 stromal interaction molecules (STIMs) are the sarcoplasmic reticulum (SR) Ca 2+ sensors that trigger store-operated Ca 2+ entry (SOCE) in a variety of cell types. While STIM1 isoform has been the focus of the research in cardiac pathophysiology, the function of the homolog STIM2 remains unknown. Using Ca 2+ imaging and patch-clamp techniques, we showed that knockdown (KD) of STIM2 by siRNAs increased SOCE and the I SOC current in neonatal rat ventricular cardiomyocytes (NRVMs). Within this cardiomyocyte model, we identified the transcript expression of Stim2.1 and Stim2.2 splice variants, with predominance for Stim2.2. Using conventional and super-resolution confocal microscopy (STED), we found that exogenous STIM2.1 and STIM2.2 formed pre-clusters with a reticular organization at rest. Following SR Ca 2+ store depletion, some STIM2.1 and STIM2.2 clusters were translocated to SR-plasma membrane (PM) junctions and co-localized with Orai1. The overexpression strategy revealed that STIM2.1 suppressed Orai1-mediated SOCE and the I SOC current while STIM2.2 enhanced SOCE. STIM2.2-enhanced SOCE was also dependent on TRPC1 and TRPC4. Even if STIM2 KD or splice variants overexpression did not affect cytosolic Ca 2+ cycling, we observed, using Rhod-2/AM Ca 2+ imaging, that Orai1 inhibition or STIM2.1 overexpression abolished the mitochondrial Ca 2+ (mCa 2+ ) uptake, as opposed to STIM2 KD. We also found that STIM2 was present in the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) by interacting with the inositol trisphosphate receptors (IP 3 Rs), voltage-dependent anion channel (VDAC), mitochondrial Ca 2+ uniporter (MCU), and mitofusin-2 (MNF2). Our results suggested that, in NRVMs, STIM2.1 constitutes the predominant functional variant that negatively regulates Orai1-generated SOCE. It participates in the control of mCa 2+ uptake capacity possibly via the STIM2-IP 3 Rs-VDAC-MCU and MNF2 complex., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the oncologic safety and quality of life associated with the use of sentinel lymph node biopsy (SLNB) as compared to elective neck dissection (END) in patients with cT1/2N0 maxillary squamous cell carcinoma., Methods: This study constituted a retrospective analysis of consecutively treated patients who underwent SLNB or END, with data collected prospectively. We analyzed the impact of the different neck procedures on regional control and disease-specific survival via the Cox model. Patients in both groups completed the University of Washington Quality of Life questionnaire., Results: We included a total of 130 patients, with 47 receiving SLNB. In all cases, the sentinel lymph node could be identified, and of these, 5 had a positive result, yielding a sensitivity of 83.3 %, a specificity of 100 %, a false negative rate of 16.7 %, and a negative predictive value of 97.6 %. The sensitivity, specificity, false negative rate, and negative predictive value of END in detecting occult metastasis were 64.3 %, 100 %, 35.7 %, and 93.2 %, respectively. In comparison to END after propensity score matching, SLNB exhibited no significant difference in its effects on regional control (p = 0.519, HR: 1.05, 95 % CI: 0.52-1.93) and disease-specific survival (p = 0.634, HR: 1.22, 95 % CI: 0.53-1.99). Patients in SLNB group showed significantly higher mean scores of shoulder and taste domains at 3 months, 6 months, and 12 months postoperatively compared to those in END group., Conclusion: SLNB could act as a viable alternative to END in cT1/2N0 maxillary squamous cell carcinoma with comparable prognosis and better quality of life., 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 development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly-l-lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability. Furthermore, the formation of physically crosslinked networks of EPL affords microneedle tips with improved formability, good mechanical properties, and amorphous nanoparticles (approximately 7.2 nm) of encapsulated DOX. As a result, a high total loading content of both antimicrobials up to 2319.1 μg/patch is achieved for efficient transdermal drug delivery. In a Pseudomonas aeruginosa-induced deep cutaneous infection model, the EPL microneedles demonstrates potent and long-term effects by synergistically enhancing antibiotic activities and prolonging drug retention in infected lesions, resulting in remarkable therapeutic efficacy with 99.91 % (3.04 log) reduction in skin bacterial burden after a single administration. Overall, our study highlights the distinct advantages of EPL microneedles and their potential in clinical antibacterial practice when loaded with amorphous DOX nanoparticles., Competing Interests: Declaration of competing interest 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 Elsevier B.V. All rights reserved.)

Background: Renal tertiary lymphoid structures (TLSs) are involved in renal pathology and prognosis of IgA nephropathy (IgAN). CD30 and its ligands participate in the formation of renal TLSs. However, the relationship between circulating CD30 and renal prognosis is unclear. The objective of this study was to evaluate the relationship between circulating CD30 and prognosis in patients with IgAN., Methods: We conducted a retrospective study including 351 patients with biopsy proved IgAN. We collected clinical and pathologic features at the time of biopsy and recorded renal follow-up outcomes. Circulating CD30 levels in IgAN patients at the time of biopsy were measured via enzyme-linked immunosorbent assay (ELISA). The association between elevated CD30 levels and the composite endpoint (defined as a ≥ 50 % decline in eGFR from baseline, end-stage renal disease, or death) was investigated using Cox regression analysis., Results: During a median follow-up period of 5.12 years, 44 (12.5 %) patients in the cohort reached the composite endpoint. Kaplan-Meier survival curve analysis revealed a significant association between higher circulating CD30 levels and a poorer renal prognosis (log-rank P < 0.001). Cox regression analysis showed that high CD30 was an independent factor for the composite endpoints in multivariable-adjusted models (HR 3.397, 95 % CI: 1.230-9.384, P = 0.018). These associations were also observed in a subgroup of patients with concomitant renal TLSs formation (10.443, 95 % CI: 1.680-65.545, P = 0.012), proteinuria > 1 g/d (HR 12.287, 95 % CI: 1.499-100.711, P = 0.019), and female patients (HR 22.372, 95 % CI: 1.797-278.520, P = 0.016)., Conclusion: Elevated level of circulating CD30 is an independent risk factor for renal disease progression in patients with IgAN., 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 B.V. All rights reserved.)

In situ NMR is a valuable tool for studying electrochemical devices, including redox flow batteries and electrocatalytic reactors, capable of detecting reaction intermediates, metastable states, time evolution of processes or monitoring stability as a function of electrochemical conditions. Here we report a parallel line detector for spatially selective in situ electrochemical NMR spectroscopy. The detector consists of 17 copper wires and is doubly tuned to 1 H/ 19 F and X nuclei ranging from 63 Cu (106.1 MHz) to 7 Li (155.5 MHz). The flat geometry of the parallel line detector allows its insertion into a high electrode surface-to-volume electrochemical flow reactor, enabling a detector-in-a-reactor design. This integrated device is named "eReactor NMR probe". Combined with B 1 -selective pulse sequences, selective detection of the nuclei at the electrode-electrolyte interface, that is within a distance of 800 μm from the electrode surface, has been achieved. The selective detection of 7 Li and 19 F nuclei is demonstrated using two electrolytes, LiCl and LiBF 4 solutions, respectively. A good B 1 homogeneity with an 810° to 90° pulse intensity ratio of 68-72 % was achieved. Using electrochemical plating of lithium metal as a model reaction, we further demonstrated the operando functionality of the probe. The new eReactor NMR probe offers a general method for studying flow electrochemistry, and we envision applications in a wide range of environmentally relevant energy systems, for example, Li metal batteries, electrochemical ammonia synthesis, carbon dioxide capture and reduction, redox flow batteries, fuel cells, water desalination, lignin oxidation etc., Competing Interests: Declaration of competing interest R. Luo, H. J. W. G. Janssen, A. P. M. Kentgens, E. W. Zhao together with Radboud Innovation (Radboud University Nijmegen) filed a patent application to protect intellectual property embedded within this report and its relation to the use of the eReactor NMR probe., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Doublecortin-like kinase 1 (DCLK1) is a microtubule-associated protein kinase involved in neurogenesis and human cancer. Recent studies have revealed a novel functional role for DCLK1 in inflammatory signaling, thus positioning it as a novel target kinase for respiratory inflammatory disease treatment. In this study, we designed and synthesized a series of NVP-TAE684-based derivatives as novel anti-inflammatory agents targeting DCLK1. Bio-layer interferometry binding screening and kinase assays of the NVP-TAE684 derivatives led to the discovery of an effective DCLK1 inhibitor (a24), with an IC 50 of 179.7 nM. Compound a24 effectively inhibited lipopolysaccharide (LPS)-induced inflammation in macrophages with higher potency than the lead compound. Mechanistically, compound a24 inhibited LPS-induced inflammation by inhibiting DCLK1-mediated IKKβ phosphorylation. Furthermore, compound a24 showed in vivo anti-inflammatory activity in an LPS-challenged acute lung injury model. These findings suggest that compound a24 may serve as a novel candidate for the development of DCLK1 inhibitors and a potential therapeutic agent for the treatment of inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lingfeng Chen reports financial support was provided by National Natural Science Foundation of China. Lingfeng Chen reports financial support was provided by Natural Science Funding of Zhejiang Province. Guang Liang reports financial support was provided by Zhejiang Provincial Key Scientific Project. If there are other authors, they 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 Inc. All rights reserved.)

Herein, a β-1,3- D -glucan based yeast cell wall loaded with co-loaded nanoparticles of Rhein (RH) and Emodin (EMO), was developed for the combined treatment of ulcerative colitis (UC) by modulating gut microbiota and the Th17/Treg cell balance. This was achieved through an oral "nano-in-micro" advanced drug delivery system. Specifically, RH was grafted onto the HA chain via disulfide bonds to synthesize a reduction-sensitive carrier material and then used to encapsulate EMO to form nanoparticles with a specific drug ratio (denoted as HA-RH/EMO NPs). As anticipated, HA-RH/EMO NPs were encased within the "nests"-yeast cell wall microparticles (YPs), efficiently reach the colon and then released gradually, this occurs mainly due to the degradation of β-1,3- D -glucan by β-glucanase. Additionally, HA-RH/EMO NPs demonstrated a significant reduction-sensitive effect in GSH stimulation evaluations and a remarkable ability to target macrophages in in vitro cell uptake studies. Notably, HA-RH/EMO NYPs reduced inflammatory responses by inhibiting the PI3K/Akt signaling pathway. Even more crucially, the oral delivery and drug combination methods significantly enhanced the regulatory effects of HA-RH/EMO NYPs on gut microbiota and the Th17/Treg balance. Overall, this research marks the first use of YPs to encapsulate two components, RH and EMO, presenting a promising therapeutic strategy for UC., 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. Published by Elsevier B.V.)

The escalating concern over conventional antibiotic resistance has emphasized the urgency in developing innovative antimicrobial agents. In recent times, metal-organic frameworks (MOFs) have garnered significant attention within the realm of antimicrobial research due to their multifaceted antimicrobial attributes, including the sustained release of intrinsic or exogenous antimicrobial components, chemodynamically catalyzed generation of reactive oxygen species (ROS), and formation of photogenerated ROS. This comprehensive review provides a thorough overview of the synthetic approaches employed in the production of MOF-based materials, elucidating their underlying antimicrobial mechanisms in depth. The focal point lies in elucidating the research advancements across various antimicrobial modalities, encompassing intrinsic component release system, extraneous component release system, auto-catalytical system, and energy conversion system. Additionally, the progress of MOF-based antimicrobial materials in addressing wound infections, osteomyelitis, and periodontitis is meticulously elucidated, culminating in a summary of the challenges and potential opportunities inherent within the realm of antimicrobial applications for MOF-based materials. STATEMENT OF SIGNIFICANCE: Growing concerns about conventional antibiotic resistance emphasized the need for alternative antimicrobial solutions. Metal-organic frameworks (MOFs) have gained significant attention in antimicrobial research due to their diverse attributes like sustained antimicrobial components release, catalytic generation of reactive oxygen species (ROS), and photogenerated ROS. This review covers MOF synthesis and their antimicrobial mechanisms. It explores advancements in intrinsic and extraneous component release, auto-catalysis, and energy conversion systems. The paper also discusses MOF-based materials' progress in addressing wound infections, osteomyelitis, and periodontitis, along with existing challenges and opportunities. Given the lack of related reviews, our findings hold promise for future MOF applications in antibacterial research, making it relevant to your journal's readership., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A hyperinflammatory response is a prominent feature of feline infectious peritonitis (FIP), but the mechanisms behind the feline infectious peritonitis virus (FIPV)-induced cytokine storm in the host have not been clarified. Studies have shown that coronaviruses encode accessory proteins that are involved in viral replication and associated with viral virulence, the inflammatory response and immune regulation. Here, we found that FIPV ORF7a gene plays a key role in viral infection and host proinflammatory responses. The recombinant FIPV strains lacking ORF7a (rQS-79Δ7a) exhibit low replication rates in macrophages and do not induce dramatic upregulation of inflammatory factors. Furthermore, through animal experiments, we found that the rQS-79Δ7a strain is nonpathogenic and do not cause symptoms of FIP in cats. Unexpectedly, after three vaccinations with rQS-79Δ7a strain, humoral and cellular immunity was increased and provided protection against virulent strains in cats, and the protection rate reaches 40%. Importantly, our results demonstrated that ORF7a is a key virulence factor that exacerbates FIPV infection and inflammatory responses. Besides, our findings will provide novel implications for future development of live attenuated FIPV vaccines., 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.)

Cyanobacterial blooms cause serious environmental issues, and plant secondary metabolites are considered as new algaecide for controlling them. Cinnamomum camphora produces a wide spectrum of terpenoids and has 4 main chemotypes, including linalool, camphor, eucalyptol and borneol chemotype. To develop the new cyanobacterial algaecide by using suitable chemotype of Cinnamomum camphora and the main terpenoids, we analyzed the terpenoid composition in the 4 chemotype extracts, evaluated the algicidal effects of the extracts and their typical monoterpenoids on Microcystis aeruginosa, and investigated the algicidal mechanism of the stronger algicidal agents. Among the 4 chemotypes, eucalyptol and borneol chemotype extracts exhibited stronger algicidal effects. In the 4 chemotype extracts, monoterpenoids were the main compounds, of which linalool, camphor, eucalyptol and borneol were the typical components. Among the 4 typical monoterpenoids, eucalyptol and borneol showed stronger algicidal effects, which killed 78.8% and 100% M. aeruginosa cells, respectively, at 1.2 mM after 48 h. In 1.2 mM eucalyptol and borneol treatments, the reactive oxygen species levels markedly increased, and the caspase-3-like activity also raised. With prolonging the treatment time, M. aeruginosa cells gradually shrank and wrinkled, and the cell TUNEL fluorescence intensity and DNA degradation gradually enhanced, indicating that the lethal mechanism is causing apoptosis-like programmed cell death (PCD). Therefore, eucalyptol and borneol chemotype extracts and their typical monoterpenoids have the potential for developing as algaecides to control cyanobacteria through triggering apoptosis-like PCD., 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 Inc. All rights reserved.)

Background: Recently, brain-computer interfaces (BCIs) have attracted worldwide attention for their great potential in clinical and real-life applications. To implement a complete BCI system, one must set up several links to translate the brain intent into computer commands. However, there is not an open-source software platform that can cover all links of the BCI chain., Method: This study developed a one-stop open-source BCI software, namely MetaBCI, to facilitate the construction of a BCI system. MetaBCI is written in Python, and has the functions of stimulus presentation (Brainstim), data loading and processing (Brainda), and online information flow (Brainflow). This paper introduces the detailed information of MetaBCI and presents four typical application cases., Results: The results showed that MetaBCI was an extensible and feature-rich software platform for BCI research and application, which could effectively encode, decode, and feedback brain activities., Conclusions: MetaBCI can greatly lower the BCI's technical threshold for BCI beginners and can save time and cost to build up a practical BCI system. The source code is available at https://github.com/TBC-TJU/MetaBCI, expecting new contributions from the BCI community., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

To develop a green and facile adsorbent for removing indoor polluted formaldehyde (HCHO) gas, the biomass porous nanofibrous membranes (BPNMs) derived from microcrystalline cellulose/chitosan were fabricated by electrospinning. The enhanced chemical adsorption sites with diverse oxygen (O) and nitrogen (N)-containing functional groups were introduced on the surface of BPNMs by non-thermal plasma modification under carbon dioxide (CO 2 ) and nitrogen (N 2 ) atmospheres. The average nanofiber diameters of nanofibrous membranes and their nanomechanical elastic modulus and hardness values decreased from 341 nm to 175-317 nm and from 2.00 GPa and 0.25 GPa to 1.70 GPa and 0.21 GPa, respectively, after plasma activation. The plasma-activated nanofibers showed superior hydrophilicity (WCA = 0°) and higher crystallinity than that of the control. The optimal HCHO adsorption capacity (134.16 mg g -1 ) of BPNMs was achieved under a N 2 atmosphere at a plasma power of 30 W and for 3 min, which was 62.42 % higher compared with the control. Pyrrolic N, pyridinic N, CO and O-C=O were the most significant O and N-containing functional groups for the improved chemical adsorption of the BPNMs. The adsorption mechanism involved a synergistic combination of physical and chemical adsorption. This study provides a novel strategy that combines clean plasma activation with electrospinning to efficiently remove gaseous HCHO., 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.)

Aging is a degenerative progress, accompanied by oxidative damage, metabolic disorders and intestinal flora imbalance. Natural macromolecular polysaccharides have shown excellent anti-aging and antioxidant properties, while maintaining metabolic and intestinal homeostasis. The molecular weight, monosaccharide composition, infrared spectrum and other chemical structure information of four Rehmannia glutinosa polysaccharides (RG50, RG70, RG90, RGB) were determined, and their free radical scavenging ability was assessed. Molecular weight and monosaccharide composition analysis exhibited that RG50 (2-72 kDa), RG70 (3.2-37 kDa), RG70 (3-42 kDa), and RGB (3.1-180 kDa) were heteropolysaccharide with significant different monosaccharide species and molar ratios. We found that RG70 had the best antioxidant activity in vitro and RG70 could enhance the antioxidant enzyme system of Caenorhabditis elegans, diminished lipofuscin and reactive oxygen species levels, up-regulate the expression of daf-16, skn-1 and their downstream genes, and down-regulate the expression of age-1. Metabolomics results showed that RG70 mainly influenced glycine, serine and threonine metabolism and citric acid cycle. 16S rRNA sequencing showed that RG70 significantly up-regulated the abundance of Lachnospiraceae&#95;NK4B4&#95;group, which were positively correlated with amino acid metabolism and energy cycling. These results suggest that RG70 may delay aging by enhancing antioxidant effects, affecting probiotics and regulating key metabolic pathways., Competing Interests: Declaration of competing interest 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 Elsevier B.V. All rights reserved.)

Objective: Anemoside B4 (AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis , inhibited influenza virus FM1 or Klebsiella pneumoniae -induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in vitro ., Methods: The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8 (CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore, label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type I IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical staining., Results: The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein (N), Spike protein (S), and 3C-like protease (3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon (IFN)-β response via the activation of retinoic acid-inducible gene I (RIG-1) like receptor (RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA metabolism., Conclusion: Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs., Competing Interests: 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., (© 2023 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Psoriasis is a common, chronic, and relapsing inflammatory skin disease characterized by hyperproliferation of keratinocytes (KCs) and infiltration of immune cells. The pathogenesis of psoriasis is complex, and the exact mechanism remains partially understood. In this study, we showed that the forkhead box family protein, FOXE1, had increased expression in lesional skins compared with nonlesional skin from patients with psoriasis. FOXE1 expression was also increased in an imiquimod-induced psoriatic mouse model as well as in M5-stimulated KCs. Using combinational approaches of knockdown and overexpression of FOXE1, we demonstrated that FOXE1 may promote the proliferation of KCs by facilitating G1/S transition and activating extracellular signal-regulated kinase 1/2 signaling pathway. In addition, knockdown of FOXE1 reduced the production of IL-1β, IL-6, and TNF-α by KCs. RNA-sequencing profiling identified WNT5A as a potential downstream effector of FOXE1. Knockdown of WNT5A inhibited the proliferation of KCs; reduced the production of IL-1β, IL-6, and TNF-α by KCs; and mitigated the growth-promoting effect of FOXE1 in FOXE1-overexpressed KCs. Finally, depletion of FOXE1 by lentiviral delivery of small hairpin RNAs or genetic approach ameliorated dermatitis symptoms in imiquimod-induced psoriasis-like mouse models. Taken together, our results indicated that FOXE1 participates in the pathogenesis of psoriasis and can serve as a target of psoriasis treatment., (Copyright © 2023. Published by Elsevier Inc.)

Three novel Co-based coordination polymers including {[Co(L)(μ 3 -O) 1/3 ] 2 } n (1), {[Co(L)(bimb)]} n (2) and {[Co(L)(bimmb) 1/2 ]} n (3) (H 2 L = 2,6-di(4-carboxylphenyl)-4-(4-(triazol-1-ylphenyl))pyridine), bimb = 1,4-bis(lmidazol) butane, bimmb = 1,4-bis(imidazole-1-ylmethyl)benzene) were successfully prepared under solvothermal conditions and characterized. Single-crystal X-ray diffraction analyses revealed that 1 possesses a 3D architecture composed of a trinuclear cluster [Co 3 N 3 (CO 2 ) 6 (μ 3 -O)], 2 exhibits a 2D new topological framework with the point symbol (8 4 ·12 2 )(8) 2 , whereas 3 shows a unique six-fold interpenetrated 3D framework with a (6 3 ·8 2 ·10) 2 (6 3 ) 2 (8) topology. Impressively, all of them can function as a highly selective and sensitive fluorescent sensor for the biomarker methylmalonic acid (MMA) via fluorescence quenching. The low detection limit, reusability and high anti-interference performance together make 1-3 become promising sensors for the practical detection of MMA. Furthermore, the successful application of MMA detection in urine sample was demonstrated, which may be a potential candidate for the further development of clinical diagnostic tools., Competing Interests: Declaration of competing interest There is no competing interest declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The frequent occurrence of extreme weather reminds us to focus more attention on sustainable development. A panel of Chinese A-share listed companies is selected as a research sample to explore how climate policy uncertainty has an effect on companies' green technology innovation. According to the empirical findings, corporate green technology innovation is negatively related to the uncertainty of climate policy. By affecting their R&D investments and risk tolerance, corporations' ability to develop in green technologies has been impacted by the uncertainty of climate policy. We also note that due to the nature of business ownership, the detrimental effect of uncertain climate policy on green technology innovation varies slightly between companies. While environmental regulations reinforce the negative impact of climate policy uncertainty, government subsidies can significantly mitigate this negative impact. These results have important theoretical and practical implications for the development of green economy theory and the realization of energy efficiency in various countries., 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 Inc. All rights reserved.)

Background: Chronic kidney disease (CKD) is a long-term condition that affects >10% of the adult population worldwide. Noninvasive assessment of renal function has important clinical significance for disease diagnosis and prognosis evaluation., Objective: To explore the value of mDIXON-Quant combined with amide proton transfer weighted (APTw) imaging for accessing renal function in chronic kidney disease (CKD)., Materials and Methods: Twenty-two healthy volunteers (HVs) and 30 CKD patients were included in this study, and the CKD patients were divided into the mild CKD (mCKD) group (14 cases) and moderate-to-severe CKD (msCKD) group (16 cases) according to glomerular filtration rate (eGFR). The cortex APT (cAPT), medulla APT (mAPT), cortex R2 ⁎ (cR2 ⁎ ), medulla R2 ⁎ (mR2 ⁎ ), cortex FF (cFF) and medulla FF (mFF) values of the right renal were independently measured by two radiologists. Intra-group correlation coefficient (ICC) test was used to test the inter-observer consistency. The analysis of variance (ANOVA) was used to compare the difference among three groups. Mann-Whitney U test was used to analyze the differences of R2 ⁎ , FF and APT values among the patient and HV groups. Area under the receiver operating characteristic (ROC) curve (AUC) was used to analyze the diagnostic efficiency. The corresponding threshold, sensitivity, and specificity were obtained according to the maximum approximate index. The combined diagnostic efficacy of R2 ⁎ , FF, and APT values was analyzed by binary Logistic regression, and the AUC of combined diagnosis was compared with the AUC of the single parameter by the Delong test., Results: The cAPT value of the HV, mCKD and msCKD groups increased gradually. The mAPT value and cR2 ⁎ values of the mCKD and msCKD groups were higher than those of the HV group, while the mFF value of the mCKD group was lower than HV group (all P < 0.05). The cAPT and mAPT values showed good diagnostic efficacy in evaluating different degrees of renal damage, while cR2 ⁎ and mFF values showed moderate diagnostic efficacy. When combining the APT, R2 ⁎ , and FF values, the diagnostic efficiency was significantly improved., Conclusion: mDIXON-Quant combined APTw imaging can be used for improved diagnosis of CKD., (Copyright © 2023. Published by Elsevier Inc.)

Immunotherapy for prostate cancer (PCa) faces serious challenges. Therefore, the co-inhibitory receptors that regulate T cell function of PCa must be elucidated. Here we identified that the inhibitory receptor LAG3 was significantly induced in T cells from PCa patients. Gene array analysis revealed that insufficient ataxia telangiectasia mutated (ATM) gene expression in PCa T cells was responsible for the elevated LAG3 expression. Mechanistically, insufficient ATM expression impaired its ability to activate AMPKα signaling and CD4 + T cell functions, which further enhances the binding of the transcription factors XBP1 and EGR2 to LAG3 promoter. Reconstitution of ATM and inhibition of XBP1 or EGR2 in PCa T cells suppressed LAG3 expression and restored the effector function of CD4 + T cells from PCa. Our study revealed the mechanism of LAG3 upregulation in CD4 + T lymphocytes of PCa patients and may provide insights for the development of immunotherapeutic strategies for PCa treatment., 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

The endocrine system is responsible for secreting and controlling hormones crucial in regulating key body activities. However, endocrine disruptors or endocrine-disrupting chemicals (EDCs) can harm human health and well-being by interfering with this complex process. This report seeks to assess the present state of understanding about endocrine disruptors in China, including their origins, impacts, and obstacles, and to provide actionable recommendations for reducing exposure and mitigating negative effects. Strong negative correlations between ANOE and rural ecological compensation (REC) and a negative correlation between ANOE and forest coverage (FC) were found in this analysis of the relationships between agricultural nitrous oxide emissions (ANOE), agricultural methane emissions (AME), and land use and land cover variables (LUPC). Just as LUPC is significantly inversely related to FC, AME is positively related. The team uses a gradient-boosted model (GBM) with a Gaussian loss function and fine-tunes the model's parameters to achieve optimal performance and reliable prediction results. With a relative relevance score of 90.36 for ANOE and 67.64 for AME, the analysis shows that LUPC is the most important factor in influencing emission levels. This study aims to increase knowledge of endocrine disruptors' potential advantages and disadvantages in outdoor exercise. The study aims to aid in preventing and managing many diseases and disorders caused by hormonal imbalances or disruptions by examining the origins, effects, and potential mitigation of these substances during outdoor activity. Safe and healthful outdoor exercise is promoted by the study's efforts to discover and implement effective and sustainable solutions to decrease emissions and exposure to endocrine disruptors. This comprehensive study aims to promote a healthier and more sustainable environment for individuals engaging in outdoor exercise by synthesizing current knowledge, providing practical recommendations, and emphasizing the importance of awareness and action., 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 Inc. All rights reserved.)

Aims: Neuroinflammation in the spinal dorsal horn (SDH) region plays an important role in the pathogenesis of interstitial cystitis (IC)/bladder pain syndrome (BPS). Oxidative stress is an important etiological factor for inflammatory diseases. This study aimed to investigate the therapeutic effects of umbilical cord mesenchymal stem cells UMSCs on neuroinflammation and oxidative stress in IC and the underlying mechanisms., Materials and Methods: Rats were intraperitoneally injected with cyclophosphamide (50 mg/kg bodyweight) to establish the IC animal model. Additionally, rats were intrathecally injected with a Sirt1-specific agonist (SRT1720; 8 μg/rat) or inhibitor (EX527; 8 μg/rat). Furthermore, rats were intrathecally injected with human UMSCs (hUMSCS; 8 × 10 5 cells/rat). Rat behavior was examined using the mechanical allodynia test, novel object recognition test, sucrose preference test, and urodynamics analysis. Neuroinflammation and oxidative stress the SDH region were examined using western blotting, immunofluorescence, enzyme-linked immunosorbent assay, and commercial kits., Key Findings: The Sirt1/Nrf2/HO-1 pathway was downregulated in IC rats. Sirt1 activation and inhibition differentially affected the behavior of IC rats. hUMSCs effectively mitigated the upregulation of oxidative stress, proinflammatory cytokines, and glial activation in the SDH region. Additionally, hUMSCs suppressed mechanical allodynia, dysregulated urodynamics, memory deficits, and depressive-like behavior in IC rats. hUMSCs exerted therapeutic effects through the Sirt1/Nrf2/HO-1 pathway., Significance: intrathecal hUMSCs injection alleviated behavioral deficits of IC rats by mitigating neuroinflammation and oxidative stress through the Sirt1/Nrf2/HO-1 pathway and can be potentially an effective therapeutic strategy for IC., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Deep learning (DL)-based denoising of low-dose positron emission tomography (LDPET) and low-dose computed tomography (LDCT) has been widely explored. However, previous methods have focused only on single modality denoising, neglecting the possibility of simultaneously denoising LDPET and LDCT using only one neural network, i.e., joint LDPET/LDCT denoising. Moreover, DL-based denoising methods generally require plenty of well-aligned LD-normal-dose (LD-ND) sample pairs, which can be difficult to obtain. To this end, we propose a self-supervised two-stage training framework named MAsk-then-Cycle (MAC), to achieve self-supervised joint LDPET/LDCT denoising. The first stage of MAC is masked autoencoder (MAE)-based pre-training and the second stage is self-supervised denoising training. Specifically, we propose a self-supervised denoising strategy named cycle self-recombination (CSR), which enables denoising without well-aligned sample pairs. Unlike other methods that treat noise as a homogeneous whole, CSR disentangles noise into signal-dependent and independent noises. This is more in line with the actual imaging process and allows for flexible recombination of noises and signals to generate new samples. These new samples contain implicit constraints that can improve the network's denoising ability. Based on these constraints, we design multiple loss functions to enable self-supervised training. Then we design a CSR-based denoising network to achieve joint 3D LDPET/LDCT denoising. Existing self-supervised methods generally lack pixel-level constraints on networks, which can easily lead to additional artifacts. Before denoising training, we perform MAE-based pre-training to indirectly impose pixel-level constraints on networks. Experiments on an LDPET/LDCT dataset demonstrate its superiority over existing methods. Our method is the first self-supervised joint LDPET/LDCT denoising method. It does not require any prior assumptions and is therefore more robust., 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. Published by Elsevier Ltd.)

The persistent transformation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (MFs) and the excessive proliferation of MF-HSCs in the liver contribute to the pathogenesis of liver fibrosis, cirrhosis, and liver cancer. Glycolysis inhibition of MF-HSCs can reverse their MF phenotype and suppress their abnormal expansion. Here, we have developed vitamin A-derivative (VA) decorated PEG-PCL polymeric micelles to encapsulate the labile and hydrophobic camptothecin (CPT) and direct its active attack on HSCs, selectively inhibiting of HIF-1α and cellular glycolysis, ultimately repressing hepatic fibrogenesis. The obtained micelles exhibited a good stability, biocompatibility, pH sensitivity, and exceptional HSC-targetability, allowing an efficient accumulation of their carried CPT in acutely and chronically injured livers. On their intracellular release of CPT specifically in MF-HSCs, these CPT micelles nicely inhibited the HIF-1α and a series of glycolytic players in MF-HSCs and prominently suppressed their proliferation and MF phenotypic characteristics. Accordingly, on in vitro administration to the mice challenged by CCl 4 or subjected to bile duct ligation, these VA-decorated CPT micelles ameliorated the pathological symptoms of the livers, as evidenced by the significant reduction in serum levels of ALT and AST, infiltration of inflammatory cells, and collagen accumulation, the drastic down-regulation of multiple fibrotic genes, and the good recovery of attenuated hepatocyte CYP2E1 and lipogenesis regulator PPARγ. Overall, the CPT carried by VA-decorated PEG-PCL polymeric micelles can selectively inhibit the glycolysis and expansion of HSCs and thus suppress fibrogenesis, providing an original and effective approach for anti-fibrotic therapy. STATEMENT OF SIGNIFICANCE: Our work introduces an innovative antifibrotic drug system that is developed upon the active targeting of CPT and aims for the fate reversal of HSCs. Through HSC-targeted delivery achieved by PEG-PCL polymeric micelles decorated with vitamin A-derivatives, CPT significantly suppressed the expressions of HIF-1α and glycolytic enzymes in MF-HSCs, as well as their pathologic expansion in mouse livers. It effectively ameliorated chronic liver fibrosis in mice induced by CCl 4 injection or BDL and restored the damaged liver structure and function. These compelling findings demonstrate the therapeutic potential of glycolytic HSC-targeting in combating fibrosis and related disorders and thus provide new promise for future clinical management of such prevalent and life-threatening conditions., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The risk of sexual transmission of HIV from individuals with low-level HIV viraemia receiving antiretroviral therapy (ART) has important public health implications, especially in resource-limited settings that use alternatives to plasma-based viral load testing. This Article summarises the evidence related to sexual transmission of HIV at varying HIV viral load levels to inform messaging for people living with HIV, their partners, their health-care providers, and the wider public., Methods: We conducted a systematic review and searched PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Conference Proceedings Citation Index-Science, and WHO Global Index Medicus, for work published from Jan 1, 2010 to Nov 17, 2022. Studies were included if they pertained to sexual transmission between serodiscordant couples at various levels of viraemia, the science behind undetectable=untransmittable, or the public health impact of low-level viraemia. Studies were excluded if they did not specify viral load thresholds or a definition for low-level viraemia or did not provide quantitative viral load information for transmission outcomes. Reviews, non-research letters, commentaries, and editorials were excluded. Risk of bias was evaluated using the ROBINS-I framework. Data were extracted and summarised with a focus on HIV sexual transmission at varying HIV viral loads., Findings: 244 studies were identified and eight were included in the analysis, comprising 7762 serodiscordant couples across 25 countries. The certainty of evidence was moderate; the risk of bias was low. Three studies showed no HIV transmission when the partner living with HIV had a viral load less than 200 copies per mL. Across the remaining four prospective studies, there were 323 transmission events; none were in patients considered stably suppressed on ART. Among all studies there were two cases of transmission when the index patient's (ie, patient with previously diagnosed HIV infection) most recent viral load was less than 1000 copies per mL. However, interpretation of both cases was complicated by long intervals (ie, 50 days and 53 days) between the transmission date and the most recent index viral load result., Interpretation: There is almost zero risk of sexual transmission of HIV with viral loads of less than 1000 copies per mL. These data provide a powerful opportunity to destigmatise HIV and promote adherence to ART through dissemination of this positive public health message. These findings can also promote access to viral load testing in resource-limited settings for all people living with HIV by facilitating uptake of alternative sample types and technologies., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests We declare no competing interests., (© 2023 World Health Organization. Published by Elsevier Ltd. All rights reserved. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

DNA methylation refers to the chemical modification process of obtaining a methyl group by the covalent bonding of a specific base in DNA sequence with S-adenosyl methionine (SAM) as a methyl donor under the catalysis of methyltransferase (MTase), which is related to the occurrence of multiple diseases. Therefore, the detection of MTase activity is of great significance for disease diagnosis and drug screening. Because reduced graphene oxide (rGO) has a unique planar structure and remarkable catalytic performance, it is not clear whether rGO can rapidly catalyze silver deposition as an effective way of signal amplification. However, in this study, we were pleasantly surprised to find that using H 2 O 2 as a reducing agent, rGO can rapidly catalyze silver deposition, and its catalytic efficiency of silver deposition is significantly better than that of GO. Therefore, based on further verifying the mechanism of catalytic properties of rGO, we constructed a novel electrochemical biosensor (rGO/silver biosensor) for the detection of dam MTase activity, which has high selectivity and sensitivity to MTase in the range of 0.1 U/mL to 10.0 U/mL, and the detection limit is as low as 0.07 U/mL. Besides, this study also used Gentamicin and 5-Fluorouracil as inhibitor models, confirming that the biosensor has a good application prospect in the high-throughput screening of dam MTase 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 Inc. All rights reserved.)

Introduction: Survival significance of parotid lymph node (LN) factors in parotid cancer remains unclear, our goal was to assess the impact of number, size, and extranodal extension (ENE) of metastatic parotid LNs on prognosis in parotid cancer., Materials and Methods: Patients with surgically treated parotid cancer were retrospectively enrolled. Primary outcome variable was recurrence-free survival (RFS) and overall survival (OS). The hazard ratios (HRs) of main predictive variables including the number, size, and ENE of positive parotid LNs on RFS and OS were analyzed using Cox model. The secondary outcome variable was ENE of metastatic parotid LN, its association with clinicopathologic variables were evaluated using Chi-square test., Results: In total, 453 patients (186 male and 267 female) were included. The 10-year RFS and OS rates were 73% (95%CI: 69%-77%) and 61% (95%CI: 55%-67%), respectively. In Cox model, compared none parotid LN metastasis, one metastatic parotid LN did not offer additional compromise of RFS (p = 0.224) or OS (p = 0.135), but two or more positive LNs decreased the control of RFS (HR: 2.017; 95%CI: 1.378-4.632) and OS (HR: 2.173; 95%CI: 1.367-4.275). When accounting for the number of metastatic LNs, LN size or ENE was no longer related to RFS or OS. ENE of parotid LN tended to develop if there was presence of T3/4 stage, lymphovascular invasion, high histologic grade, N2/3 stage, and three or more positive parotid LNs., Conclusion: Quantitative parotid LN burden but not ENE or LN size is an important determinant of survival in patients with parotid cancer., 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, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: Trust is an essential part of the physician-patient relationship. Yet physicians' perspectives in physician-patient trust has always been ignored, and the concept has not yet been clearly defined and analyzed. This study explores the conceptual understanding of physicians' trust in patients in the context of healthcare and clinical practice and provides a theoretical frameworks foundation for practitioners and researchers., Methods: Seven databases were systematically searched for relevant studies, including Pubmed, CINAHL, ScienceDirect, Web of Science, CNKI, Wanfang and Weipu. Walker and Avant's approach to concept analysis was performed to extract the concept attributes, antecedents, consequences, and define empirical referents., Results: Of the 8028 articles identified, 43 met the inclusion criteria. Five core attributes were identified: (a) Interaction and support; (b) Confidence and expectation in building trust; (c) Motivation for medical treatment; (d) Socially and medically epistemic competence of patients; (e) Self-reported accuracy. Antecedents were divided into a physician-patient relationship and the social context of medicine. Consequences included treatment outcomes, patient outcomes, and treatment efficiency for physicians and patients., Conclusions: Our findings offer insights into refining the concept of trust. By collaborating across healthcare trusts, we can contribute to the development of theoretical models and empirical research. This concept analysis serves as a foundation to develop instruments to measure the concept and highlight the need to design a qualitative study and enhancement strategy for physician trust in patients., Practice Implications: Trust in Physicians' perspectives is an essential part of the physician-patient relationship. Establishing and strengthening physicians' trust in patients is significant to healthcare and clinical practice. Concept analysis of physicians' trust in patients will give policymakers a more evident concept and understanding of the importance of the trust improvement strategy and guide healthcare managers to improve theoretical development., 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. Published by Elsevier B.V.)

Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer. NPTX2, a member of the neuronal pentraxin family, is reported to play inconsistent roles in different cancers. The role and mechanism of NPTX2 in cSCC remain unclear. In this study, we found that NPTX2 was overexpressed in both skin lesions and cell lines of cSCC. In vitro studies showed that NPTX2 facilitated cell proliferation, migration, invasion, colony formation, and epithelial‒mesenchymal translation in A431 and SCL-1 cells. NPTX2 interacted with METTL3, increased METTL3 expression, and improved N6-methyladenosine modification in cSCC cell lines. Mechanistically, NPTX2 facilitated epithelial‒mesenchymal translation by promoting METTL3-mediated N6-methyladenosine of SNAIL. METTL3 knockdown and N6-methyladenosine inhibition reversed the impacts of NPTX2 overexpression on cSCC cells. In vivo studies verified the role of NPTX2 as an oncogene in cSCC. Therefore, NPTX2 may be a potential therapeutic target for cSCC., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Underwater endoscopic mucosal resection (UEMR) is an emerging technique for endoscopic resection of superficial non-ampullary duodenal epithelial tumors (SNADETs). However, compared to conventional EMR, its efficacy and safety has not been widely explored., Methods: We conducted a comprehensive search using the Pubmed, Embase, and Cochrane Library databases to identify studies comparing the efficacy and safety of UEMR versus EMR for SNADETs. The main outcomes examined included en bloc resection rate, R0 resection rate, recurrence rate, procedure time, and adverse events., Results: A total of 5 studies comprising 635 patients were included. All the literature included duodenal lesions smaller than 20 mm. The pooled analysis showed that UEMR could achieve a higher en bloc resection rate (OR 1.78, 95%CI: 1.17 to 2.71, P = 0.007) and shorter procedure time (MD -4.08, 95%CI: -6.44 to -1.73, P = 0.0007) than EMR. However, the pooled results did not support a superiority of UEMR over EMR for R0 resection rate (OR 1.27; 95% CI: 0.90 to 1.81, P = 0.18) or recurrence rate (OR 0.49; 95% CI: 0.15 to 1.67, P = 0.26). The occurrence of adverse events, including postoperative bleeding, intraoperative perforation, and delayed perforation, was very low in included studies., Conclusion: Compared to EMR, UEMR is an effective and safe technique for SNADETs ≤20 mm., Competing Interests: Declaration of Competing Interest Drs. Xiu-He Lv, Rong Luo, Qing Lu, Kai Deng, and Jin-Lin Yang have no conflicts of interest or financial ties to disclose., (Copyright © 2022. Published by Elsevier Ltd.)

Aims: Lung squamous cell carcinoma (LUSC) causes over 400,000 deaths annually, yet it lacks targeted therapy. A major antagonist of Hedgehog pathway, HHIP (Hedgehog Interacting Protein) plays an important role in LUSC; however, the regulatory mechanism remains unclear. Long non-coding RNA HHIP-AS1 plays suppressive or promotive roles in different cancers, but its role in LUSC remains unknown. This manuscript is to investigate regulatory mechanism of HHIP and the role of HHIP-AS1 in LUSC., Main Methods: Precision-cut lung slices (PCLS) from human LUSC samples are cultured to mimic LUSC growth. Overexpression and knockdown in multiple LUSC cell lines and PCLS are achieved by lentivirus infection. Transcriptome profile and lung cancer activity are evaluated by RNA-sequencing, immunostaining and CCK8 assay etc. KEY FINDINGS: HHIP is regulated independently of Hh pathway in LUSC. Additionally, downregulation of HHIP-AS1 is associated with poor prognosis. Consistently, HHIP-AS1 inhibits LUSC growth by suppressing cell proliferation and migration. Transcriptome profiling of HHIP-AS1 knockdown (KD) cells uncovered HHIP downregulation. Interestingly, a comparison between the transcriptomes of HHIP-AS1 KD or HHIP KD cells manifested high similarity. Subsequently it's confirmed that HHIP-AS1 regulates HHIP in LUSC cells. Notably, HHIP-AS1 regulation on LUSC growth is achieved through stabilizing HHIP mRNA rather than regulating MIR-153-3P/PCDHGA9 or MIR-425-5P/DNYC1I2. Finally, it's confirmed in PCLS from human LUSC samples that HHIP-AS1 suppresses LUSC via regulating HHIP mRNA., Significance: This study uncovers HHIP-AS1 as a novel tumor suppressor in LUSC and provides new insights into the molecular regulation of LUSC, which will help developing new therapeutic strategies., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pharmacologically active natural products have played a significant role in the history of drug development. They have acted as sources of therapeutic drugs for various diseases such as cancer and infectious diseases. However, most natural products suffer from poor water solubility and low bioavailability, limiting their clinical applications. The rapid development of nanotechnology has opened up new directions for applying natural products and numerous studies have explored the biomedical applications of nanomaterials loaded with natural products. This review covers the recent research on applying plant-derived natural products (PDNPs) nanomaterials, including nanomedicines loaded with flavonoids, non-flavonoid polyphenols, alkaloids, and quinones, especially their use in treating various diseases. Furthermore, some drugs derived from natural products can be toxic to the body, so the toxicity of them is discussed. This comprehensive review includes fundamental discoveries and exploratory advances in natural product-loaded nanomaterials that may be helpful for future clinical development., 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.)

The antioxidant enzymes play the crucial role in inhibiting mutton spoilage. In this study, visible near-infrared (Vis-NIR) hyperspectral imaging (HSI) combined with entropy weight method (EWM) was developed for the first time to evaluate the antioxidant properties of Tan mutton. The comprehensive index of antioxidant enzymes (AECI) consisting of peroxidase (49.34%), catalase (37.97%) and superoxidase (12.69%) was constructed by the EWM. Partial least squares regression, least squares support vector machine and artificial neural networks (ANN) were developed based on characteristic wavelengths extracted by successful projections algorithm, uninformative variable selection, iteratively retains informative variables (IRIV), regression coefficient and competitive adaptive reweighted sampling (CARS). The textural features (TF) were extracted by the gray level co-occurrence matrix and fused with the spectral data to establish models. Visualization of the changes in antioxidant enzyme activity was constructed from the optimal model. In addition, two-dimensional correlation spectra (2D-COS) with AECI as a perturbation variable was used to identify spectral features, revealing chemical bond changes order under the characteristic peaks at 612-799-473-708-559 nm. The results showed that the IRIV-CARS-TF-ANN model performed the best, with prediction set coefficient of determination (R P ) of 0.8813, which improved 2.12%, 1.11% and 2.77% over the R 2 ) of 0.8813, which improved 2.12%, 1.11% and 2.77% over the R P 2 of full band, IRIV and IRIV-CARS, respectively. It was suggested that fusion data of HSI may effectively predict the activity of antioxidant enzymes in Tan mutton., 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. Published by Elsevier B.V.)

Curcumin (CUR) is a promising natural compound in ulcerative colitis (UC) treatment, but limited by its low oral bioavailability and poor targeting ability. Therefore, given the targeting action of lactoferrin (LF) by binding to the LF receptors of intestinal epithelial cells (IECs) and of folic acid (FA) by binding to the FA receptors of macrophages, we developed an oral dual-targeting nanosystem. Laminarin (LA)-coated, FA-modified LF nanoparticles (NPs) were used to encapsulate CUR (LA/FA/CUR-NPs) with a food-grade, enzyme-sensitive, and dual-targeting capacity. For the generated NPs, LF improved the loading efficiency of CUR (95.08 %). The LA layer could improve the upper gastrointestinal tract stability of the NPs while improve drug release around colon lesion through β-glucanase digestion. Based on the cellular uptake evaluation, FA/CUR-NPs were capable of specifically targeting colonic epithelial cells and macrophages through LF and FA ligands, respectively, to enhance the uptake efficiency. Moreover, based on the advantage of the dual-targeting strategy, oral administration of FA/CUR-NPs obviously reduced colitis symptoms by alleviating inflammation, accelerating colonic mucosal barrier repair and restoring the balance of the intestinal microbiota. This dual-targeted nanodesign corresponded to the multi-bioresponsibilities of CUR, thus offering a promising approach in UC treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Ganoapplins A and B (1 and 2) with a 6/6/6/5/6-fused pentacyclic skeleton containing an aromatic E ring, were obtained from Ganoderma applanatum. Their structures were established through extensive spectroscopic analyses, quantum chemical calculations, including calculated chemical shifts with DP4 + analysis and electronic circular dichroism (ECD). A plausible biosynthetic pathway for 1 and 2 was proposed. Furthermore, their roles in activating autophagy were investigated and the cellular assays showed that 1 and 2 can inhibit tau pathology by inducing autophagy, suggesting their potential against Alzheimer's disease (AD)., 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 Inc. All rights reserved.)

Objectives: The effectiveness of oseltamivir versus peramivir in children infected with influenza remains unclear. This study aimed to evaluate their effectiveness in young children (aged 0-5 years) infected with severe influenza A virus (IAV) or influenza B virus (IBV)., Methods: We analyzed a cohort of 1662 young children with either IAV (N = 1095) or IBV (N = 567) who received oseltamivir or peramivir treatment from January 1, 2018 to March 31, 2022. Propensity score matching methods were applied to match children who were oseltamivir-treated versus peramivir-treated., Results: Children who were IAV-infected and IBV-infected shared similar features, such as influenza-associated symptoms and comorbidities at baseline. Among children infected with IAV with bacterial coinfection, the recovery rate was significantly greater in children treated with oseltamivir than in children treated with peramivir (15.6% vs 4.4%, P = 0.01). The median duration of hospitalization was also shorter in children treated with oseltamivir. Among children infected with IAV without bacterial coinfection, the recovery rate was greater in children treated with oseltamivir than in children treated with peramivir (21.1% vs 3.7%, P = 0.002). However, oseltamivir and peramivir offered similar recovery rates and duration of hospitalization (P >0.05 for both) among children infected with IBV., Conclusion: Oseltamivir and peramivir exhibit similar effectiveness in young children with severe influenza B, whereas oseltamivir demonstrated improved recovery and shorter hospitalization in the treatment of severe influenza A in hospitalized children., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Non-destructive preservation state estimation is an essential prerequisite for the preservation and conservation of waterlogged archaeological wooden artifacts. Herein, Near Infrared (NIR) spectroscopy coupled with orthogonal partial least squares discriminant analysis (OPLS-DA) were applied to assess sixty-four waterlogged archaeological woods collected from seven excavation sites in the period range of 2900 BCE-1912 CE, aiming at developing a non-destructive, accurate and rapid preservation state estimation methodology. The role of non-decayed recent wood of relevant species on preservation state estimation was studied in prior, showing the use of non-decayed recent wood could not improve the predictive ability. Besides, the high variability in terms of chemical structure between archaeological softwoods and archaeological hardwoods did affect the preservation state estimation. Thus, a simple OPLS-DA model of non-destructively distinguishing archaeological hardwoods from softwoods, R 2 X cum of 0.659, R 2 Y cum of 0.836 and Q 2 of 0.763, was established to avoid and overcome destructive approach for wood identification. Then, the well-defined three grouped separations of slightly-decayed, moderately-decayed and severely-decayed waterlogged archaeological woods were revealed in OPLS-DA models, providing R cum of 0.763, was established to avoid and overcome destructive approach for wood identification. Then, the well-defined three grouped separations of slightly-decayed, moderately-decayed and severely-decayed waterlogged archaeological woods were revealed in OPLS-DA models, providing R 2 of 0.793, R cum of 0.793, R 2 Y cum of 0.680, and R 2 cum of 0.780, R 2 X cum of 0.780, R 2 Y cum of 0.901, Q 2 cum of 0.870, for waterlogged archaeological hardwoods and waterlogged archaeological softwoods respectively. Potential predictive wood spectral bands were screened and tentatively identified as hydroxyls of crystalline cellulose, acetyl groups of hemicelluloses, C-H bands of lignin, which guaranteed the elimination of non-structural compounds, such as water and inorganic components interference. Furthermore, the developed NIR methodology was validated by an extensively used destructive method consisting of anatomical characteristics, maximum water content and basic density analyses. The results indicated that NIR coupled to chemometrics could non-destructively and accurately predict the preservation states of waterlogged archaeological wooden artifacts and avoid the interference of water and inorganic deposits., 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 B.V. All rights reserved.)

Dysregulation of CDK6 plays crucial roles in the carcinogenesis of many kinds of human malignancies. However, the role of CDK6 in esophageal squamous cell carcinoma (ESCC) is not well known. We investigated the frequency and prognostic value of CDK6 amplification to improve the risk stratification in patients with ESCC. Pan-cancer analysis of CDK6 was conducted on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases. CDK6 amplification was detected in 502 ESCC samples by Fluorescence in situ hybridization (FISH) through tissue microarrays (TMA). Pan-cancer analysis revealed that CDK6 mRNA level was much higher in multiple kinds of cancers and higher CDK6 mRNA level indicated a better prognosis in ESCC. In this study, CDK6 amplification was detected in 27.5% (138/502) of patients with ESCC. CDK6 amplification was significantly correlated with tumor size (p = 0.044). Patients with CDK6 amplification tended to have a longer disease-free survival (DFS) (p = 0.228) and overall survival (OS) (p = 0.200) compared with patients without CDK6 amplification but of no significance. When further divided into I-II and III-IV stage, CDK6 amplification was significantly associated with longer DFS and OS in III-IV stage group (DFS, p = 0.036; OS, p = 0.022) rather than in I-II stage group (DFS, p = 0.776; OS, p = 0.611). On univariate and multivariate analysis of Cox hazard model, differentiation, vessel invasion, nerve invasion, invasive depth, lymph node metastasis and clinical stage were significantly associated with DFS and OS. Moreover, invasion depth was an independent factor for ESCC prognosis. Taken together, for ESCC patients in III-IV stage, CDK6 amplification indicated a better prognosis., 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. Published by Elsevier Ltd.)

The measurement of illicit drugs in wastewater is increasingly being adopted as a method for objective monitoring of population-level illicit drug use. This work describes the first small-volume direct-injection ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of 11 illicit drugs and metabolites in wastewater. The method required an injection volume of only 30 µL of wastewater sample, the limits of detection (LOD) ranged from 0.4 ng/L to 2 ng/L and the lower limits of quantitation (LLOQ) ranged from 1 ng/L to 5 ng/L. Application of the method to real wastewater samples collected from wastewater treatment plants revealed morphine in all samples, together with other illicit drugs (methamphetamine, codeine, ketamine, and nor-ketamine) in some samples. Small-volume direct injection showed great potential as an efficient method for the high-throughput determination of illicit drugs in wastewater., 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 B.V. All rights reserved.)