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Background: Corticosteroids are among the few effective treatments for knee osteoarthritis, but short duration of action limits their utility. EP-104IAR, a long-acting formulation of fluticasone propionate for intra-articular injection, optimises the action of fluticasone propionate through novel diffusion-based extended-release technology. The SPRINGBOARD trial assessed the efficacy, safety, and pharmacokinetics of EP-104IAR in people with knee osteoarthritis., Methods: SPRINGBOARD was a randomised, vehicle-controlled, double-blind, phase 2 trial done at 12 research sites in Denmark, Poland, and Czech Republic. We recruited adults aged 40 years or older with primary knee osteoarthritis (Kellgren-Lawrence grade 2-3) who reported Western Ontario and McMaster Universities Osteoarthritis Arthritis Index (WOMAC) pain scores of at least 4 and no more than 9 out of 10. Participants were randomly assigned (1:1) to receive one intra-articular dose of 25 mg EP-104IAR or vehicle control. Randomisation was done via interactive web-based access to a central predefined computer-generated list with block size of six (allocated by clinical site). Participants and assessors were masked to treatment allocation. Participants were followed up for 24 weeks. The primary outcome was the difference between groups in change in WOMAC pain score from baseline to week 12, analysed in all participants who were randomly assigned and received treatment. Safety, including laboratory analyses, and pharmacokinetics from quantification of fluticasone propionate in peripheral blood were assessed in all participants who received a dose of randomly assigned treatment. A person with lived experience of knee osteoarthritis was involved in study interpretation and writing of the report. This trial is registered with ClinicalTrials.gov, NCT04120402, and the EU Clinical Trials Register, EudraCT 2021-000859-39, and is complete., Findings: Between Sept 10, 2021, and Nov 16, 2022, 1294 people were screened for eligibility, and 319 were randomly assigned to EP-104IAR (n=164) or vehicle control (n=155). One participant in the EP-104IAR group was excluded from all analyses because treatment was not administered due to an adverse event. 318 participants (135 [42%] male and 183 [58%] female, 315 [99%] White) received randomly assigned treatment and were included in the primary analysis and safety analysis (EP-104IAR, n=163; vehicle control, n=155). At week 12, least squares mean change in WOMAC pain score from baseline was -2·89 (95% CI -3·22 to -2·56) in the EP-104IAR group and -2·23 (-2·56 to -1·89) in the vehicle control group, with a between-group difference of -0·66 (-1·11 to -0·21; p=0·0044); a significant between-group difference persisted to week 14. 106 (65%) of 163 participants in the EP-104IAR group had one or more treatment-emergent adverse event compared with 89 (57%) of 155 participants in the vehicle control group. Effects on serum glucose and cortisol concentrations were minimal and transient. There were no treatment-emergent deaths or treatment-related serious adverse events. Plasma concentrations of fluticasone propionate showed a blunted initial peak with terminal half-life of approximately 18-20 weeks., Interpretation: These phase 2 results suggest that EP-104IAR has the potential to offer clinically meaningful pain relief in knee osteoarthritis for an extended period of up to 14 weeks, longer than published data for currently marketed corticosteroids. There were minimal effects on glucose and cortisol, and stable fluticasone propionate concentrations in plasma. The safety and efficacy of EP-104IAR will be further evaluated in phase 3 trials, including the possibility of bilateral and repeat dosing with EP-104IAR., Funding: Eupraxia Pharmaceuticals., Translation: For the Danish translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests JH, AM, MMK, CD, and VP are employees of Eupraxia Pharmaceuticals. SLB, HR, and KM are or were employees of Sanos Clinics who were contracted by Eupraxia Pharmaceuticals to perform the clinical research. ACM, YL, CPM, and ARB are employees of NBCD, a contract research organisation contracted by Eupraxia Pharmaceuticals to perform data management and trial management. PGC has performed speakers' bureaus or consultancies for AbbVie, AstraZeneca, Eli Lilly, Eupraxia, Galapagos, Genascence, GSK, Grunenthal, Janssen, Levicept, Medipost, Merck, Moebius, Novartis, Sandoz, Stryker, TrialSpark, and UCB. MW is on the Board of Directors for Eupraxia Pharmaceuticals and received royalties from NextStep Arthropedix. LSS declares no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The biological activities of heparan sulfate (HS) are intimately related to their molecular weights, degree and pattern of sulfation and homogeneity. The existing methods for synthesizing homogeneous sugar chains of low dispersity involve multiple steps and require stepwise isolation and purification processes. Here, we designed a mesoporous metal-organic capsule for the encapsulation of glycosyltransferase and obtained a microreactor capable of enzymatically catalyzing polymerization reactions to prepare homogeneous heparosan of low dispersity, the precursor of HS and heparin. Since the sugar chain extension occurs in the pores of the microreactor, low molecular weight heparosan can be synthesized through space-restricted catalysis. Moreover, the glycosylation co-product, uridine diphosphate (UDP), can be chelated with the exposed metal sites of the metal-organic capsule, which inhibits trans-cleavage to reduce the molecular weight dispersity. This microreactor offers the advantages of efficiency, reusability, and obviates the need for stepwise isolation and purification processes. Using the synthesized heparosan, we further successfully prepared homogeneous 6-O-sulfated HS of low dispersity with a molecular weight of approximately 6 kDa and a polydispersity index (PDI) of 1.032. Notably, the HS generated exhibited minimal anticoagulant activity, and its binding affinity to fibroblast growth factor 1 was comparable to that of low molecular weight heparins., Competing Interests: Declaration of competing interest We declare that we 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 cutaneous lymphatic system regulates tissue inflammation, fluid balance and immunological responses. Lymphangiogenesis or lymphatic dysfunction may lead to lymphedema, immune deficiency, chronic inflammation etc. Tissue regeneration and healing depend on angiogenesis and lymphangiogenesis during wound healing. Tissue oedema and chronic inflammation can slow wound healing due to impaired lymphangiogenesis or lymphatic dysfunction. For example, impaired lymphangiogenesis or lymphatic dysfunction has been detected in nonhealing wounds such as diabetic ulcers, venous ulcers and bedsores. This review summarizes the structure and function of the cutaneous lymphatic vessel system and lymphangiogenesis in wounds. Furthermore, we review wound lymphangiogenesis processes and remodelling, especially the influence of the inflammatory phase. Finally, we outline how to control lymphangiogenesis to promote wound healing, assess the possibility of targeting lymphangiogenesis as a novel treatment strategy for chronic wounds and provide an analysis of the possible problems that need to be addressed., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Unplanned reoperation (URO) after surgery adversely affects the quality of life and prognosis of patients undergoing anterior resection for rectal cancer. This study aims to meet the urgent need for reliable predictive tools by developing an optimized machine learning model to estimate the risk of URO following anterior resection in rectal cancer patients., Methods: This retrospective study collected multidimensional data from patients who underwent anterior resection for rectal cancer at Tongji Hospital of Huazhong University of Science and Technology from January 2012 to December 2022. Feature selection was conducted using both least absolute shrinkage and selection operator (LASSO) regression and the Boruta algorithm. Multiple machine learning models were developed, with parameter optimization via grid search and cross-validation. Performance metrics included accuracy, specificity, sensitivity, and area under curve (AUC). The optimal model was interpreted using SHapley Additive exPlanations (SHAP), and an online platform was created for real-time risk prediction., Results: A total of 2384 patients who underwent anterior resection for rectal cancer were included in this study. Following rigorous selection, 14 variables were identified for constructing the machine learning model. The optimized model demonstrated high predictive accuracy, with the random forest (RF) model achieving the best overall performance. The model achieved an AUC of 0.889 and an accuracy of 0.842 on the test dataset. SHAP analysis revealed that the tumor location, previous abdominal surgery, and operative time were the most significant factors influencing the risk of URO., Conclusion: This study developed an optimized machine learning-based online predictive system to assess the risk of URO after anterior resection in rectal cancer patients. Accessible at https://yangsu2023.shinyapps.io/UROrisk/, this system improves prediction accuracy and offers real-time risk assessment, providing a valuable tool that may support clinical decision-making and potentially improve the prognosis of rectal cancer patients., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Mesoporous metal‒organic frameworks (MOFs) are promising supports for the immobilization of enzymes, yet their applications are often limited by small pore apertures that constrain the size of encapsulated enzymes to below 5 nm. In this study, we introduced labile linkers (4,4',4''-(2,4,6-boroxintriyl)-tribenzoate, TBTB) with dynamic boroxine bonds into mesoporous PCN-333, resulting in PCN-333-TBTB with enhanced enzyme loading and protection capabilities. The selective breaking of B-O bonds creates defects in PCN-333, which effectively expands both window and cavity sizes, thereby unlocking hidden mesopores for enzyme encapsulation. Consequently, this strategy not only increases the adsorption kinetics of small enzymes (<5 nm) such as cytochrome c (Cyt C) and horseradish peroxidase (HRP), but also enables the immobilization of various large-sized enzymes (>5 nm), such as glycoenzymes. The glycoenzymes@PCN-333-TBTB platform was successfully applied to synthesize thirteen complex oligosaccharides and polysaccharides, demonstrating high activity and enhanced enzyme stability. The dynamic linker-mediated enzyme encapsulation strategy enables the immobilization of enzymes exceeding the inherent pore size of MOFs, thus broadening the scope of enzymatic catalytic reactions achievable with MOF materials., (© 2024 Wiley‐VCH GmbH.)

Objective: To assess the association between early initiation of parenteral nutrition (PN) and body growth in preterm infants with very low birth weight (VLBW)., Design: Causal inference analysis with confounders preselected by causal diagram based on the NeoNutriNet cohort containing data of infants born between 2011 and 2014 from 13 hospitals from 5 continents., Patients: Neonates with birth weight ≤1500 g., Interventions: PN initiated within the first day of life (early PN) versus within day 2-5 (delayed PN)., Main Outcome Measures: The primary outcome was body weight z-scores at postmenstrual age (PMA) 36 weeks or early discharge or death, whichever comes first (WT z-score END). Secondary outcomes included WT z-scores at week 1 and 4 of life (WT z-scores CA1 and CA4), corresponding growth velocities (GVs), mortality and incidence of necrotising enterocolitis (NEC), and duration and episodes of antibiotic treatment., Results: In total, 2151 infants were included in this study and 2008 infants were in the primary outcome analysis. Significant associations of early PN were found with WT z-score END (adjusted mean difference, 0.14 (95% CI 0.05 to 0.23)), CA4 (β, 0.09 (0.04 to 0.14)) and CA1 (0.04 (0.01 to 0.08)), and GV PMA 36 weeks (1.02 (0.46 to 1.58)) and CA4 (1.03 (0.56 to 1.49), all p<0.001), but not with GV CA1 (p>0.05). No significant associations with mortality, incidence of NEC or antibiotic use was found (all p>0.05)., Conclusions: For VLBW infants, PN initiated within the first day of life is associated with improved in-hospital growth., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the mechanisms behind the effects of acupuncture in Traditional Chinese Medicine, we delved into the adenosine triphosphate/peripheral purinergic P2X receptor 3 (ATP/P2X3) receptor signaling system as an indicator of the body's energy state, commonly referred to as " Qi "., Methods: The tail-flick test was utilized to explore the impact of acupuncture on pain tolerance threshold (PTT) in mice, while also assessing adenosine (ADO) levels and adenylate energy charge (EC) at Zusanli (ST36). The study further investigated the dose-dependent effects of acupuncture on PTT and ADO levels at Zusanli (ST36). To shed light on the underlying mechanisms of acupuncture's effects, the study examined the impact of ATP, a P2X3 receptor antagonist, and adenosine disodium on PTT following acupuncture administration., Results: Acupuncture at Zusanli (ST36) led to significant improvements in PTT in mice, with the most effective interventions being twirling for 2 min and needle retention for 28 min. These interventions also resulted in significant increases in ATP levels. The effects of acupuncture were further augmented by administration of different doses of ATP at Zusanli (ST36), and pretreatment with a P2X3 receptor antagonist decreased PTT. Adenylate EC peaked at 30 min after intraperitoneal injection of ATP, and pretreatment with various doses of i.p. ATP 30 min prior to acupuncture increased PTT in a dose-dependent manner. Additionally, pretreatment with an i.p. or intramuscular injection of adenosine disodium enhanced the effects of acupuncture., Conclusion: This research provides compelling evidence that ATP is involved in the regulation of PTT through acupuncture, revealing new avenues for achieving enhanced clinical outcomes.

The development of a low-cost and efficient oxygen evolution reaction (OER) electrode is of critical importance for water electrolysis technologies. The general approach to achieving a high-efficiency OER electrode is to regulate catalytic material structures by synthetic control. Here we reported an orthogonal approach to obtaining the OER electrode without intentional design and synthesis, namely, recycling MnO 2 cathodes from failed rechargeable aqueous batteries and investigating them as ready-made catalytic electrodes. The recycled MnO 2 cathode showed very little Zn 2+ storage capacity but surprisingly high OER activity with a low overpotential of 307 mV at 10 mA cm -2 and a small Tafel slope of 77.9 mV dec -1 , comparable to the state-of-the-art RuO 2 catalyst (310 mV, 86.9 mV dec -1 ). In situ electrochemical and theoretical studies jointly revealed that the accelerated OER kinetics of the recycled MnO 2 electrode was attributed to the enlarged active surface area of MnO 2 and optimized electronic structure of Mn sites. This work suggests failed battery cathodes as successful catalysis electrodes for sustainable energy development.

Background: The conversion from a temporary to a permanent stoma (PS) following rectal cancer surgery significantly impacts the quality of life of patients. However, there is currently a lack of practical preoperative tools to predict PS formation. The purpose of this study is to establish a preoperative predictive model for PS using machine learning algorithms to guide clinical practice., Methods: In this retrospective study, we analyzed clinical data from a total of 655 patients who underwent anterior resection for rectal cancer, with 552 patients from one medical center and 103 from another. Through machine learning algorithms, five predictive models were developed, and each was thoroughly evaluated for predictive performance. The model with superior predictive accuracy underwent additional validation using both an independent testing cohort and the external validation cohort. The Shapley Additive exPlanations (SHAP) approach was employed to elucidate the predictive factors influencing the model, providing an in-depth visual analysis of its decision-making process., Results: Eight variables were selected for the construction of the model. The support vector machine (SVM) model exhibited superior predictive performance in the training set, evidenced by an AUC of 0.854 (95 % CI:0.803-0.904). This performance was corroborated in both the testing set and external validation set, where the model demonstrated an AUC of 0.851 (95%CI:0.748-0.954) and 0.815 (95%CI:0.710-0.919), respectively, indicating its efficacy in identifying the PS., Conclusions: The model(https://yangsu2023.shinyapps.io/psrisk/) indicated robust predictive performance in identifying PS after anterior resection for rectal cancer, potentially guiding surgeons in the preoperative stratification of patients, thus informing individualized treatment plans and improving patient outcomes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (© 2024 Elsevier Ltd, BASO ∼ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Chemotherapy is a crucial treatment for colorectal tumors. However, its efficacy is restricted by chemoresistance. Recently, Golgi dispersal has been suggested to be a potential response to chemotherapy, particularly to drugs that induce DNA damage. However, the underlying mechanisms by which Golgi dispersal enhances the capacity to resist DNA-damaging agents remain unclear. Here, we demonstrated that DNA-damaging agents triggered Golgi dispersal in colorectal cancer (CRC), and cancer stem cells (CSCs) possessed a greater degree of Golgi dispersal compared with differentiated cancer cells (non-CSCs). We further revealed that Golgi dispersal conferred resistance against the lethal effects of DNA-damaging agents. Momentously, Golgi dispersal activated the Golgi stress response via the PKCα/GSK3α/TFE3 axis, resulting in enhanced protein and vesicle trafficking, which facilitated drug efflux through ABCG2. Identification of Golgi dispersal indicated an unexpected pathway regulating chemoresistance in CRC., (© 2024. The Author(s).)

To improve the retention and slow-release abilities of nitrogen (N) and phosphorus (P), an 82 %-purity struvite fertilizer (MAP-BC) was synthesized using magnesium-modified biochar and a solution with a 2:1 concentration ratio of NH 4 + to PO 4 3- at a pH of 8. Batch microscopic characterizations and soil column leaching experiments were conducted to study the retention and slow-release mechanisms and desorption kinetics of MAP-BC. The slow-release mechanism revealed that the dissolution rate of high-purity struvite was the dominant factor of NP slow release. The re-adsorption of NH 4 + and PO 4 3- by biochar and unconsumed MgO prolonged slow release. Mg 2+ ionized by MgO could react with PO 4 3- released from struvite to form Mg 3 (PO 4 ) 2 . The internal biochar exhibited electrostatic attraction and pore restriction towards NH 4 + , while magnesium modification and nutrient loading formed a physical antioxidant barrier that ensured long-term release. The water diffusion experiment showed a higher cumulative release rate for PO 4 3- compared to NH 4 + , whereas in soil column leaching, the trend was reversed, suggesting that soil's competitive adsorption facilitated the desorption of NH 4 + from MAP-BC. During soil leaching, cumulative release rates of NH 4 + and PO 4 3- from chemical fertilizers were 3.55-3.62 times faster than those from MAP-BC. The dynamic test data for NH 4 + and PO 4 3- in MAP-BC fitted the Ritger-Peppas model best, predicting release periods of 163 days and 166 days, respectively. The leaching performances showed that MAP-BC reduced leaching solution volume by 5.58 % and significantly increased soil large aggregates content larger than 0.25 mm by 24.25 %. The soil nutrients retention and pH regulation by MAP-BC reduced leaching concentrations of NP. Furthermore, MAP-BC significantly enhanced plant growth, and it is more suitable as a NP source for long-term crops. Therefore, MAP-BC is expected to function as a long-term and slow-release fertilizer with the potential to minimize NP nutrient loss and replace part of quick-acting fertilizer., 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: To investigate plastic surgery repair's effects and adverse reactions in the clinical therapy of asymmetric double eyelids., Methods: All 126 sufferers who came to the hospital for asymmetric double eyelid plastic repair from January 2022 to October 2022 were selected as the research objects, and they were divided into a control group and an observation group using the random number method, with 63 cases in each group, in which sufferers in the control group underwent full incision blepharoplasty and sufferers in the observation group underwent small incision liposuction with submerged sutures. The general data, treatment results, treatment satisfaction, related surgical indicators, and frequency of adverse reactions of the 2 groups of sufferers with asymmetric double eyelid plastic repair were compared., Results: It had no statistically obvious distinction between the control group and the observation group of sufferers in terms of general data such as sex, age, weight, and height (P>0.05); the total therapy efficiency of the sufferers in the observation group (95.24%) was greater than the control group (74.60%), with P value <0.05; the total treatment satisfaction of the patients in the observation group (96.83%) was significantly higher than that in the control group (76.19%), with P value <0.05; compared with the control group, patients in the observation group had shorter operative time and healing time and less intraoperative bleeding, with P value <0.05; the total frequency of adverse reactions of sufferers in the observation group (4.76%) was less than the control group (17.46%), with P value <0.05., Conclusion: Small incision liposuction with submerged sutures for plastic repair has significant efficacy, relatively high patient satisfaction, and low incidence of adverse reactions, in line with patient esthetic review, which has a broad clinical application prospect., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Mutaz B. Habal, MD.)

In the present study, a novel silane coupling agent, designated INSi, was synthesized via a facile synthetic route, incorporating indole-functional moieties. This agent was further employed for the surface modification of homemade silica nanomicrospheres (SMPs). The ensuing nanomicrosphere composite, denoted as SiO 2 @IN, exemplified pronounced interfacial π-π interactions. Optimization of the reaction conditions was conducted using the response surface optimization technique. Subsequent validation of interfacial π-π interactions was accomplished through a synergistic approach, integrating theoretical calculations and comprehensive analyses of spectral and morphological attributes exhibited by the SiO 2 @IN.

Background: Assessing diet quality has been challenging, and the associations of diet quality and daily free sugar intake with depressive and/or anxiety symptoms have shown inconsistency., Methods: A total of 1749 students aged 12-16 years were recruited using stratified random cluster sampling across three cities in China. The overall Global Dietary Recommendations (GDR) score, a novel indicator of diet quality, was constructed using the low-burden Diet Quality Questionnaire. Free sugar intake, including from beverages and foods, was measured using the Food Frequency Questionnaire. Daily free sugar intake was divided into low, medium, and high categories based on the latest version of the dietary guidelines for Chinese residents. Binomial and multinominal logistic regression analyses were used to examine the associations of the overall GDR score and daily free sugar intake categories or different sources of free sugar intake with depressive and/or anxiety symptoms., Results: The overall GDR score was negatively associated with depressive symptoms (adjusted odds ratio[aOR] = 0.92, 95%CI: 0.87-0.98) and anxiety symptoms (0.95, 0.90-0.99), particularly with comorbid depression and anxiety (0.90, 0.84-0.97). Conversely, daily free sugar intake was positively associated with symptoms of depression and/or anxiety, the multiple aOR for symptoms depression or anxiety were significantly increased with higher daily free sugar intake (all P trend  < 0.05). Both free sugar from beverages and from foods were positively associated with depressive and/or anxiety symptoms. These associations were consistent between males and females., Limitations: Cross-sectional design and self-reported symptoms., Conclusions: Diet quality was negatively associated with symptoms of depression or anxiety, especially with comorbid symptoms among adolescents. Daily free sugar intake, regardless of its sources, was positively associated with symptoms of depression and/or anxiety., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interests., (Copyright © 2024. Published by Elsevier B.V.)

Seawater electrolysis presents a promising avenue for green hydrogen production toward a carbon-free society. However, the electrode materials face significant challenges including severe chlorine-induced corrosion and high reaction overpotential, resulting in low energy conversion efficiency and low current density operation. Herein, we put forward a nanoporous nickel (npNi) cathode with high chlorine corrosion resistance for energy-efficient seawater electrolysis at industrial current densities (0.4-1 A cm -2 ). With the merits of an electrostatic chlorine-resistant surface, modulated Ni active sites, and a robust three-dimensional open structure, the npNi electrode showed a low hydrogen evolution reaction overpotential of 310 mV and a high electricity-hydrogen conversion efficiency of 59.7% at 400 mA cm -2 in real seawater and outperformed most Ni-based seawater electrolysis cathodes in recent publications and the commercial Ni foam electrode (459 mV, 46.4%) under the same test condition. In situ electrochemical impedance spectroscopy, high-frame-rate optical microscopy, and first-principles calculation revealed that the improved corrosion resistance, enhanced intrinsic activity, and mass transfer were responsible for the lowered electrocatalytic overpotential and enhanced energy efficiency.

Objectives: In this study, we describe the patterns of antibiotic prescription for neonates based on World Health Organization's (WHO) Essential Medicines List Access, Watch, and Reserve (AWaRe), and the Management of Antibiotic Classification (MAC) Guidelines in China., Methods: One-day point-prevalence surveys (PPS) on antimicrobial prescriptions were conducted on behalf of hospitalized neonates in China from September 1 and November 30, annually from 2017 to 2019., Results: Data was collected for a total of 2674 neonatal patients from 15 hospitals in 9 provinces across China of which 1520 were newborns who received at least one antibiotic agent. A total of 1943 antibiotic prescriptions were included in the analysis. The most commonly prescribed antibiotic was meropenem (11.8%). The most common reason for prescribing antibiotic to neonates was pneumonia (44.2%). There were 419 (21.6%), 1343 (69.1%) and 6 (0.3%) antibiotic prescriptions in the Access, Watch and Reserve groups, respectively. According to MAC Guidelines in China, there were 1090 (56.1%) antibiotic agents in the Restricted and 414 (21.3%) in the Special group., Conclusion: Broad-spectrum antibiotics included in the Watch and Special groups were likely to be overused in Chinese neonates., (© 2024. The Author(s).)

Importance: In China, parental labor migration often leaves children behind and is potentially adversely associated with children's health. However, the association between parental migration and aggression among their offspring remains largely underexplored., Objective: To investigate the associations of parental labor migration with total and subtypes of aggression among their offspring as well as potential sex differences therein., Design, Setting, and Participants: This cross-sectional study was conducted from February to October 2015 among students aged 11 to 20 years from 45 public middle and high schools across 5 provinces of China. Data analysis was performed from December 1, 2022, to August 1, 2023., Exposures: Parental migration, including migration status (yes or no), pattern (father, mother, or both), and the child's age at the initial parent-child separation., Main Outcomes and Measures: Total and subtypes of aggression (including physical aggression [PA], verbal aggression [VA], indirect aggression [IA], anger, and hostility) were measured using the Chinese version of the Buss-Warren Aggression Questionnaire. Binomial logistic regression analyses were used separately to estimate adjusted odds ratios (aORs) and 95% CIs of parental migration by total and subtypes of aggression., Results: A total of 15 301 participants (7900 [51.6%] male and 7401 [48.4%] female) aged 11 to 20 years (mean [SD] age, 15.1 [1.8] years) were included. Of these participants, 5961 (39.0%) experienced parental migration; 2451 (16.0%) met the criteria for total aggression, 2407 (15.7%) for PA, 2283 (14.9%) for VA, 2899 (18.9%) for IA, 2307 (15.1%) for anger, and 2564 (16.8%) for hostility. Parental migration was associated with total aggression (aOR, 1.11; 95% CI, 1.01-1.22); no significant association between parental migration and subtypes of aggression was found except for PA (aOR, 1.14; 95% CI, 1.03-1.25). Compared with children whose parents did not migrate, the aORs for total aggression and PA for participants whose father migrated were 1.12 (95% CI, 1.01-1.28) and 1.15 (95% CI, 1.03-1.29), respectively; for participants with both parents having migrated, the aORs were 1.16 (95% CI, 1.02-1.31) and 1.12 (95% CI, 1.04-1.24), respectively. Compared with children whose parents did not migrate, children who experienced initial separation from 1 or both parents at adolescence had an aOR for total aggression of 1.20 (95% CI, 1.04-1.36), children who experienced initial separation from 1 or both parents at school age or adolescence had an aOR for PA of 1.15 (95% CI, 1.01-1.32) and 1.26 (95% CI, 1.04-1.51), respectively. No sex differences were found in these associations., Conclusions and Relevance: In this cross-sectional study of Chinese children and adolescents, we found that parental migration, mainly of the father or both parents or an initial separation at adolescence or school age from 1 or both parents, was associated with higher odds of total aggression and PA among offspring. These associations were similar between male and female participants.

Background: Myelodysplastic syndrome (MDS) is known to arise through the pathogenic bone marrow mesenchymal stem cells (MSC) by interacting with hematopoietic stem cells (HSC). However, due to the strong heterogeneity of MDS patients, it is difficult to find common targets in studies with limited sample sizes. This study aimed to describe sequential molecular changes and identify biomarkers in MSC of MDS transformation., Methods: Multidimensional data from three publicly available microarray and TCGA datasets were analyzed. MDS-MSC was further isolated and cultured in vitro to determine the potential diagnostic and prognostic value of the identified biomarkers., Results: We demonstrated that normal MSCs presented greater molecular homogeneity than MDS-MSC. Biological process (embryonic skeletal system morphogenesis and angiogenesis) and pathways (p53 and MAPK) were enriched according to the differential gene expression. Furthermore, we identified HOXB3 and HOXB7 as potential causative genes gradually upregulated during the normal-MDS-AML transition. Blocking the HOXB3 and HOXB7 in MSCs could enhance the cell proliferation and differentiation, inhibit cell apoptosis and restore the function that supports hematopoietic differentiation in HSCs., Conclusion: Our comprehensive study of gene expression profiling has identified dysregulated genes and biological processes in MSCs during MDS. HOXB3 and HOXB7 are proposed as novel surrogate targets for therapeutic and diagnostic applications in MDS., (© 2024. The Author(s).)

Fungal infections have emerged as a major concern among immunocompromised patients, causing approximately 2 million deaths each year worldwide. However, the regulatory mechanisms underlying antifungal immunity remain elusive and require further investigation. The E3 ligase Trim26 belongs to the tripartite motif (Trim) protein family, which is involved in various biological processes, including cell proliferation, antiviral innate immunity, and inflammatory responses. Herein, we report that Trim26 exerts protective antifungal immune functions after fungal infection. Trim26-deficient mice are more susceptible to fungemia than their wild-type counterparts. Mechanistically, Trim26 restricts inflammatory neutrophils infiltration and limits proinflammatory cytokine production, which can attenuate kidney fungal load and renal damage during Candida infection. Trim26-deficient neutrophils showed higher proinflammatory cytokine expression and impaired fungicidal activity. We further demonstrated that excessive neutrophils infiltration in the kidney was because of the increased production of chemokines CXCL1 and CXCL2, which are mainly synthesized in the macrophages or dendritic cells of Trim26-deficient mice after Candida albicans infections. Together, our study findings unraveled the vital role of Trim26 in regulating antifungal immunity through the regulation of inflammatory neutrophils infiltration and proinflammatory cytokine and chemokine expression during candidiasis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Brain metastases (BMs) are the most frequent intracranial tumours associated with poor clinical outcomes. Radiotherapy is essential in the treatment of these tumours, although the optimal radiation strategy remains controversial. The present study aimed to assess whether whole brain radiation therapy with a simultaneous integrated boost (WBRT + SIB) provides any therapeutic benefit over WBRT alone., Methods: We included and retrospectively analysed 82 patients who received WBRT + SIB and 83 who received WBRT alone between January 2012 and June 2021. Intracranial progression-free survival (PFS), local tumour control (LTC), overall survival (OS), and toxicity were compared between the groups., Results: Compared to WBRT alone, WBRT + SIB improved intracranial LTC and PFS, especially in the lung cancer subgroup. Patients with high graded prognostic assessment score or well-controlled extracranial disease receiving WBRT + SIB had improved intracranial PFS and LTC. Moreover, WBRT + SIB also improved the long-term intracranial tumour control of small cell lung cancer patients. When evaluating toxicity, we found that WBRT + SIB might slightly increase the risk of radiation-induced brain injury, and that the risk increased with increasing dosage. However, low-dose WBRT + SIB had a tolerable radiation-induced brain injury risk, which was lower than that in the high-dose group, while it was comparable to that in the WBRT group., Conclusions: WBRT + SIB can be an efficient therapeutic option for patients with BMs, and is associated with improved intracranial LTC and PFS. Furthermore, low-dose WBRT + SIB (biologically effective dose [BED] ≤ 56 Gy) was recommended, based on the acceptable risk of radiation-induced brain injury and satisfactory tumour control., Trial Registration: Retrospectively registered., (© 2023. The Author(s).)

MXenes, as a typical graphene-like material, excels in the realm of humidity sensing owing to its two-dimensional layer structure, high electrical conductivity, tunable chemical properties, hydrophilicity, and large specific surface area. This study proposed a quartz crystal microbalance (QCM) humidity sensor using a nanochitin/Ti 3 C 2 T x MXene composite as a humidity-sensing material. The morphology, nanostructure, and elemental composition of nanochitin, Ti 3 C 2 T x MXene, and nanochitin/Ti 3 C 2 T x MXene composite materials were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. Compared to the pure Ti 3 C 2 T x MXene-coated QCM humidity sensor, the nanochitin/Ti 3 C 2 T x MXene-coated QCM humidity sensor exhibited a higher sensitivity (20.54 Hz/%RH) in the humidity range of 11.3% to 97.3%. The nanochitin/Ti 3 C 2 T x Mxene-coated QCM humidity sensor also demonstrated low humidity hysteresis (2.12%RH), very fast response/recovery times (4.4/4.1 s), a high quality factor (37 k), and excellent repeatability and sustained stability over time. Eventually, a bimodal exponential kinetics adsorption model was utilized for the analysis of the response mechanism of the nanochitin/Ti 3 C 2 T x MXene composite material-based QCM humidity sensor. This study provides new ideas for optimizing the moisture-sensitive performance of MXene-based QCM humidity sensors.

Many studies have shown that magnesium modified biochar (MgBC) can recover nutrients from wastewater and be applied as an excellent slow-release fertilizer in farmland. However, the recovery products (NP-loaden MgBC), represented by struvite or magnesium phosphate, have a high degree of self-alkalinity, which may significantly increase the ammonia (NH 3 ) volatilization in farmland. In this study, the optimal adsorption parameters, self-alkaline regulation process and co-adsorption mechanism of MgBC for ammonium ion (NH 4 + ) and phosphate ion (PO 4 3- ) were studied through batch experiments. A field experiment was conducted with three treatments, including local conventional fertilization (N 1 B 0 ) and the application of 5 t·ha -1 or 10 t·ha -1 NP-loaden MgBC in combination with local conventional fertilization (N 1 B 1 and N 1 B 2 , respectively), to determine the impact of NP-loaden MgBC on NH 3 volatilization, surface water c(NH 4 + -N) and pH. The results indicated that the maximum NH 4 + and PO 4 3- synergistic recovery of MgBC under the optimal adsorption parameters (dosage of 0.6 g·L -1 ; initial NH 4 + and PO 4 3- concentrations of 120 and 60 mg·L -1 and pH of 8) were 59.96 and 98.60 mg·g -1 , respectively. Self-regulating alkaline MgBC maintained pH suitable for struvite, and precipitation mechanism controlled the adsorption. The presence of NP-loaden MgBC raised the pH levels in surface water during the basal fertilization stage and increased c(NH 4 + -N) in surface water during the topdressing stages. This, in turn, led to a significant increase in NH 3 volatilization loss during the entire rice-growing period, with N 1 B 1 and N 1 B 2 experiencing a 23.87 % and 48.91 % increase respectively, compared to N 1 B 0 . Therefore, it is imperative to take into account the adverse impact of NP-laden MgBC on NH 3 loss in paddy fields when considering its application in future field studies., 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.)

Background: Benign anastomotic strictures (BAS) significantly impact patients' quality of life and long-term prognosis. However, the current clinical practice lacks accurate tools for predicting BAS. This study aimed to develop a machine-learning model to predict BAS in patients with rectal cancer who have undergone anterior resection., Methods: Data from 1973 patients who underwent anterior resection for rectal cancer were collected. Multiple machine learning classification models were integrated to analyze the data and identify the optimal model. Model performance was evaluated using receiver operator characteristic (ROC) curves, decision curve analysis (DCA), and calibration curves. The Shapley Additive exPlanation (SHAP) algorithm was utilized to assess the impact of various clinical characteristics on the optimal model to enhance the interpretability of the model results., Results: A total of 10 clinical features were considered in constructing the machine learning model. The model evaluation results indicated that the random forest (RF)model was optimal, with the area under the test set curve (AUC: 0.888, 95% CI: 0.810-0.965), accuracy: 0.792, sensitivity: 0.846, specificity: 0.791. The SHAP algorithm analysis identified prophylactic ileostomy, operative time, and anastomotic leakage as significant contributing factors influencing the predictions of the RF model., Conclusion: We developed a robust machine-learning model and user-friendly online prediction tool for predicting BAS following anterior resection of rectal cancer. This tool offers a potential foundation for BAS prevention and aids clinical practice by enabling more efficient disease management and precise medical interventions., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (© 2023 Published by Elsevier Ltd.)

This article focuses on an attempt to classify and recognize the characterized images of EEG signals directly. For EEG signals, the recognition and judgment of different signals has been the key direction of research. CNN (Convolutional Neural Network) models are usually used for recognition of EEG raw signals about movement and Imagery Dataset. However, the images of EEG raw signals are basically unreadable for researchers, so characterization is a common tool. However, direct recognition of the characterized images is a relatively empty area in the existing research because it requires much higher machine performance than the traditional raw signal recognition. However, feeding the extracted feature images into a CNN and training them can be an efficient and intuitive response to the potential of EEG for brain mapping. The main goal of this research is to examine the discriminative capabilities of traditional visual and image neural networks for pictures described by EEG data. This is not typical in contemporary brain-computer interface research. The direct recognition of the described photos uses a lot of GPU (graphics computing unit) resources, but for the characterized images are easier for people to read than the original images. This work indicates the viability of direct research on defined pictures and increases the application scenario of EEG signals.

Osteoporosis is a prevalent bone disorder characterized by low bone mineral density (BMD) and deteriorated bone microarchitecture, leading to an increased risk of fractures. Vitamin D (VD), an essential nutrient for skeletal health, plays a vital role in maintaining bone homeostasis. The biological effects of VD are primarily mediated through the vitamin D receptor (VDR), a nuclear receptor that regulates the transcription of target genes involved in calcium and phosphate metabolism, bone mineralization, and bone remodeling. In this review article, we conduct a thorough literature search of the PubMed and EMBASE databases, spanning from January 2000 to September 2023. Utilizing the keywords "vitamin D," "vitamin D receptor," "osteoporosis," and "therapy," we aim to provide an exhaustive overview of the role of the VD/VDR system in osteoporosis pathogenesis, highlighting the most recent findings in this field. We explore the molecular mechanisms underlying VDR's effects on bone cells, including osteoblasts and osteoclasts, and discuss the impact of VDR polymorphisms on BMD and fracture risk. Additionally, we examine the interplay between VDR and other factors, such as hormonal regulation, genetic variants, and epigenetic modifications, that contribute to osteoporosis susceptibility. The therapeutic implications of targeting the VDR pathway for osteoporosis management are also discussed. By bringing together these diverse aspects, this review enhances our understanding of the VD/VDR system's critical role in the pathogenesis of osteoporosis and highlights its significance as a potential therapeutic target., (© 2023. The Author(s).)

Association of greenness surrounding school with aggression among adolescents was not well understood. This study aimed to investigate the associations of greenness surrounding school with adolescents' total and sub-types of aggression and explore potential mediators underlying these associations. A multi-site study of 15,301 adolescents aged 11-20 years were recruited through a multistage, random cluster sampling across 5 representative provinces in mainland China. Satellite-derived Normalized Difference Vegetation Index (NDVI) values within circular buffers of 100 m, 500 m, and 1000 m surrounding school were used to indicate the adolescents' greenness exposure. We used the Chinese version of Buss and Warren's Aggression Questionnaire to assess total and sub-types of aggression. Daily concentrations of PM 2.5, and NO 2 were obtained from the China High Air Pollutants datasets. Per IQR increment of NDVI 100 m and 500 m surrounding school was associated with lower odds of total aggression; odds ratio [OR] with 95% CI was 0.958 (0.926-0.990) for the 100 m buffer and 0.963 (0.932-0.996) for the 500 m buffer, respectively. Similar associations can be observed in two sub-types of aggression, including verbal (NDVI 100 m: 0.960 (0.925-0.995); NDVI500m: 0.964 (0.930-0.999)) and indirect aggression (NDVI 100 m: 0.956 (0.924-0.990); NDVI500m: 0.953 (0.921-0.986)). There were no sex and age differences in the associations of school surrounding greenness with aggression, except that the beneficial associations of greenness exposure with total aggression (0.933(0.895-0.975) vs.1.005(0.956-1.056)), physical aggression (0.971(0.925-1.019) vs.1.098(1.043-1.156)), and hostility (0.942(0.901-0.986) vs.1.016(0.965-1.069)) were greater among participants aged ≥16 years than those aged<16 years. PM 2.5 (proportion mediated estimates: 0.21; 95% CI: 0.08, 0.94) and NO 2 (-0.78, 95% CI: -3.22, -0.37) mediated the association of NDVI 500 m surrounding school with total aggression. Our data indicated that exposure to greenness in school surroundings was associated with reduced aggression, particularly in verbal and indirect aggression. The presence of PM 2.5 and NO 2 partially mediated these associations., 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.)

Human acellular amniotic membrane (HAAM) has emerged as a promising tool in the field of regenerative medicine, particularly for wound healing and tissue regeneration. HAAM provides a natural biological scaffold with low immunogenicity and good anti-infective and anti-scarring results. Despite its potential, the clinic application of HAAM faces challenges, particularly with respect to the preparation methods and its low mechanical strength. This review provides a comprehensive overview of HAAM, covering its preparation, sterilization, preclinical research, and clinical applications. This review also discusses promising decellularization and sterilization methods, such as Supercritical Carbon Dioxide (SC-CO 2 ), and the need for further research into the regenerative mechanisms of HAAM. In addition, we discuss the potential of HAAM as a skin dressing and cell delivery system in preclinical research and clinical applications. Both the safety and effectiveness of HAAM have been validated by extensive research, which provides a robust foundation for its clinical application.

Background & Aims: Gut immaturity leads to feeding difficulties in very preterm infants (<32 weeks gestation at birth). Maternal milk (MM) is the optimal diet but often absent or insufficient. We hypothesized that bovine colostrum (BC), rich in protein and bioactive components, improves enteral feeding progression, relative to preterm formula (PF), when supplemented to MM. Aim of the study is to determine whether BC supplementation to MM during the first 14 days of life shortens the time to full enteral feeding (120 mL/kg/d, TFF120)., Methods: This was a multicenter, randomized, controlled trial at seven hospitals in South China without access to human donor milk and with slow feeding progression. Infants were randomly assigned to receive BC or PF when MM was insufficient. Volume of BC was restricted by recommended protein intake (4-4.5 g/kg/d). Primary outcome was TFF120. Feeding intolerance, growth, morbidities and blood parameters were recorded to assess safety., Results: A total of 350 infants were recruited. BC supplementation had no effect on TFF120 in intention-to-treat analysis [n (BC) = 171, n (PF) = 179; adjusted hazard ratio, aHR: 0.82 (95% CI: 0.64, 1.06); P = 0.13]. Body growth and morbidities did not differ, but more cases of periventricular leukomalacia were detected in the infants fed BC (5/155 vs. 0/181, P = 0.06). Blood chemistry and hematology data were similar between the intervention groups., Conclusions: BC supplementation during the first two weeks of life did not reduce TFF120 and had only marginal effects on clinical variables. Clinical effects of BC supplementation on very preterm infants in the first weeks of life may depend on feeding regimen and remaining milk diet., Trial Registration: http://www., Clinicaltrials: gov: NCT03085277., Competing Interests: Conflict of Interest The study received support from a Danish company, Biofiber-Damino, which donated the bovine colostrum used for the study. University of Copenhagen holds a patent (Eur. Patent no. EP2858653A1) on the use of bovine colostrum for preterm infants. Per Torp Sangild is listed as the sole inventor but has declined any share of potential revenue arising from commercial exploitation of such a patent. All other authors have no conflicts of interest. All funding bodies had no role in the design, analysis or writing of this article., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Coronary artery disease (CAD) is one of the main types of cardiovascular disease and is characterized by myocardial ischemia as a result of narrowing of the coronary arteries., Objective: To evaluate the impact of chronic obstructive pulmonary disease (COPD) on outcomes in patients with CAD treated by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)., Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library for observational studies and post-hoc analyses of randomized controlled trials published before Jan 20, 2022, in English. Adjusted odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) for short-term outcomes (in-hospital and 30-day all-cause mortality) and long-term outcomes (all-cause mortality, cardiac death, major adverse cardiac events) were extracted or transformed., Results: Nineteen studies were included. The risk of short-term all-cause mortality was significantly higher in patients with COPD than in those without COPD (RR 1.42, 95% CI 1.05-1.93), as were the risks of long-term all-cause mortality (RR 1.68, 95% CI 1.50-1.88) and long-term cardiac mortality (HR 1.84, 95% CI 1.41-2.41). There was no significant between-group difference in the long-term revascularization rate (HR 1.01, 95% CI 0.99-1.04) or in short-term and long-term stroke rates (OR 0.89, 95% CI 0.58-1.37 and HR 1.38, 95% CI 0.97-1.95). Operation significantly affected heterogeneity and combined results for long-term mortality (CABG, HR 1.32, 95% CI 1.04-1.66; PCI, HR 1.84, 95% CI 1.58-2.13)., Conclusions: COPD was independently associated with poor outcomes after PCI or CABG after adjustment for confounders., 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: Both internet addiction (IA) and non-suicidal self-injury (NSSI) are major public health concerns among adolescents, however, the association between IA and NSSI was not well understood. We aimed to investigate the association between IA and NSSI within a cohort study, and explore the mediated effect of depressive symptoms and the moderating effect of social support in the association., Methods: A total of 1530 adolescents aged 11-14 years who completed both the baseline (T1) and 14-month follow-up (T2) survey of the Chinese Adolescent Health Growth Cohort were included for the current analysis. IA, NSSI, depressive symptoms and social support were measured at T1; depressive symptoms and NSSI were measured again at T2. Structural equation models were employed to estimate the mediated effect of depressive symptoms and the moderating effect of social support in the association between IA and NSSI at T2., Results: IA was independently associated with an increased risk of NSSI at T2, with the total effect of 0.113 (95%CI 0.055-0.174). Depressive symptoms mediated the association between IA and NSSI at T2, and social support moderated the indirect but not the direct effect of IA on NSSI at T2. Sex differences were found on the mediated effect of depressive symptoms and the moderated mediation effect of social support., Conclusions: Interventions that target adolescents' NSSI who also struggle with IA may need to focus on reducing depressive symptoms and elevating social support., (© 2023. The Author(s).)

Acinetobacter baumannii (A. baumannii) is a common nosocomial pathogen associated with serious clinical challenges owing to its rapidly increasing resistance to antibiotics. Due to their high host specificity and easy access to the natural environment, bacteriophages (phages) may serve as good antibacterial agents. Phage therapy has been successfully used to treat antibiotic-resistant A. baumannii infections. As a fundamental step before phage therapy, the characterization and sequencing of A. baumannii phages have been well studied. Until October 2022, 132 A. baumannii phages have been sequenced and studied, with their genomes ranging from 4 to 234 kb, and we summarize the characterized and sequenced A. baumannii phages. This review is a current and short overview that does not go into detail on the A. baumannii phages. In addition, preclinical studies and clinical applications of A. baumannii phages are also included., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The purpose of our study was to investigate the association of obesity status change with hypertension onset based on a community-based longitudinal cohort study in North China., Methods: This longitudinal study included 3,581 individuals free of hypertension at baseline in the first survey (2011-2012). All participants were followed up (2018-2019). According to the criteria, a total of 2,618 individuals were collected for analysis. We used adjusted Cox regression models and Kaplan-Meier survival analysis to estimate the association between obesity status change and hypertension onset. Additionally, we applied the forest plot to visualize the subgroup analysis including age, gender, and the differences in some variables between baseline and follow-up. Finally, we conducted a sensitivity analysis to examine the stability of our results., Results: Over nearly 7 years of follow-up, a total of 811 (31%) developed hypertension. The new hypertension incidence was mostly observed in those who were obese all the time ( P for trend < 0.01). In the fully adjusted Cox regression model, being obese all the time increased the risk of hypertension by 30.10% [HR 4.01 (95% CI 2.20-7.32)]. The Kaplan-Meier survival analysis revealed the change in obesity status as an important feature to predict the occurrence of hypertension. Sensitivity analysis shows a consistent trend between the change in obesity status and hypertension onset in all populations. Subgroup analysis showed that age above 60 years was an important risk factor for hypertension onset, that men were more likely than women to develop hypertension, and that weight control was beneficial in avoiding future hypertension in women. There were statistically significant differences in ΔBMI, ΔSBP, ΔDBP, and ΔbaPWV between the four groups, and all variables, except baPWV changes, increased the risk of future hypertension., Conclusion: Our study shows that obese status was notably associated with a significant risk of hypertension onset among the Chinese community-based cohort., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cai, Zhao, Dong, Zhang, Wang, Wang, Zhou, Zhou, Li, Wang, Liu and Hu.)

According to the World Health Organization, antibiotic resistance is a global health threat. Of particular importance are infections caused by multidrug-resistant Gram-negative bacteria including Escherichia coli , Acinetobacter baumannii , Klebsiella pneumoniae , and Pseudomonas aeruginosa for which limited treatment options exist. Multiple and simultaneously occurring resistance mechanisms including outer membrane impermeability, overexpression of efflux pumps, antibiotic-modifying enzymes, and modification of genes and antibiotic targets have made antibiotic drug development more difficult against these pathogens. One strategy to cope with these challenges is the use of outer membrane permeabilizers that increase the intracellular concentration of antibiotics when used in combination. In some circumstances, this approach can rescue antibiotics from resistance or repurpose currently marketed antibiotics. Tobramycin-based hybrid antibiotic adjuvants that combine two outer membrane-active components have been previously shown to potentiate antibiotics by facilitating transit through the outer membrane, resulting in increased antibiotic accumulation within the cell. Herein, we extended the concept of tobramycin-based hybrid antibiotic adjuvants to tobramycin-based chimeras by engineering up to three different membrane-active antibiotic warheads such as tobramycin, 1-(1-naphthylmethyl)-piperazine, ciprofloxacin, and cyclam into a central 1,3,5-triazine scaffold. Chimera 4 (TOB-TOB-CIP) consistently synergized with ciprofloxacin, levofloxacin, and moxifloxacin against wild-type and fluoroquinolone-resistant P. aeruginosa . Moreover, the susceptibility breakpoints of ceftazidime, aztreonam, and imipenem were reached using the triple combination of chimera 4 with ceftazidime/avibactam, aztreonam/avibactam, and imipenem/relebactam, respectively, against β-lactamase-harboring P. aeruginosa . Our findings demonstrate that tobramycin-based chimeras form a novel class of antibiotic potentiators capable of restoring the activity of antibiotics against P. aeruginosa .

Thyroid cancer is a major endocrine tumor and represents an emerging health problem worldwide. MicroRNAs (miRNAs) have been addressed to participate in the pathogenesis and progression of thyroid cancer. However, it remains largely unknown what functions miR-30d may exert on thyroid cancer. This study, herein, aimed to identify the functional significance and machinery of miR-30d in the progression of thyroid cancer. MiR-30b presented aberrant low expression and ubiquitin-specific protease 22 (USP22) exhibited aberrant high expression in thyroid cancer tissues and cells. The current study proposed the possible machinery that miR-30d could target and negatively regulate USP22. Additionally, USP22 could enhance the stability of SIRT1 by inducing deubiquitination which consequently contributed to FOXO3a deacetylation-induced PUMA repression. Responding to the gain- or loss-of-function of miR-30d and/or USP22, behaviors of thyroid cancer cells were altered. Accordingly, miR-30d inhibited proliferation and promoted apoptosis of thyroid cancer cells by suppressing USP22 through SIRT1/FOXO3a/PUMA axis. The effects of miR-30d and USP22-mediated SIRT1/FOXO3a/PUMA axis on thyroid tumorigenesis were finally validated in murine models. We ultimately confirmed the anti-proliferative and pro-apoptotic effect of miR-30d via suppressing USP22 through in vivo findings. Conclusively, our findings highlight that the occurrence and progression of thyroid cancer can be suppressed by miR-30d-mediated inhibition of USP22 via the SIRT1/FOXO3a/PUMA axis, which provides a attractive therapeutic target for thyroid cancer treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Infertility is a common and rapidly growing health issue around the world. The genetic analysis based on the infertile population is crucial for intervention and treatment., Objective: To find candidate gene locus led to azoospermia in Chinese multi-ethnic groups and provide theoretical guidance for the diagnosis of genetic diseases to progressively aggravated infertility patients and sterile offspring with ART., Methods: The study based on whole-exome sequencing (WES) was presented for genetic characteristic analysis of multi-ethnics and identification of variants related to infertility in Xinjiang area of China., Results: The frequency of pathogenic variants showed significant ethnic differences among four main ethnics in Xinjiang. The population structure analysis confirmed that the Hui was close to the Han population, the Kazak was close to the Uygur population, and there are three ancestry components in the four ethnics. In addition, ten candidate variants potentially regulated azoospermia were detected, and KNTC1 (rs7968222: G > T) was chosen to validate the association. Through the analysis in the valid group, the frequency of rs7968222 (G > T) has a significant difference in the azoospermia population (11.76%, 8/68) and normospermia population (4.63%, 35/756) (P < 0.001). Interestingly, the proportion of people with abnormal follicle-stimulating hormone (FSH) level in the group carrying rs7968222 (G > T) was significantly higher than non-carriers (P < 0.05). Therefore, rs7968222 may regulate spermatogenesis through affecting hormone level., Conclusion: Our study establishes the genetics analysis of Northwest China and finds a candidate gene locus KNTC1 (rs7968222: G > T), which is one of the genetic susceptibility factors for male azoospermia., (© 2022. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Bitterness is one of the basic tastes, and sensing bitterness plays a significant role in mammals recognizing toxic substances. The bitter taste of food and oral medicines may decrease consumer compliance. As a result, many efforts have been made to mask or decrease the bitterness in food and oral pharmaceutical products. The detection of bitterness is critical to evaluate how successful the taste-masking technology is, and many novel taste-sensing systems have been developed on the basis of various interaction mechanisms. In this review, we summarize the progress of bitterness response mechanisms and the development of novel sensors in detecting bitterness ranging from commercial electronic devices based on modified electrodes to micro-type sensors functionalized with taste cells, polymeric membranes, and other materials in the last two decades. The challenges and potential solutions to improve the taste sensor quality are also discussed.

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that may lead to bone erosion and disability. Although there are many biological therapies in RA treatment nowadays, such as etanercept and tofacitinib, there are still a considerable number of patients who cannot achieve clinical deep remission, which makes patients feel pain and stiffness of joints. As a traditional Chinese medicine preparation, Wangbi granule showed a synergistic role with methotrexate in the treatment of RA patients with "kidney deficiency and dampness" or "stasis blocking channels". Therefore, it is a promising therapeutic strategy for the clinical deep remission of RA. In this study, Wangbi granule will be used as the test drug. The investigators conduct this study to evaluate the efficacy and safety of Wangbi granule in the treatment of patients who have not achieved deep remission despite the use of methotrexate and tofacitinib., Methods and Analysis: Two parallel randomized, triple-blind, placebo-controlled trials will be conducted. In six study centers, 340 eligible RA patients will be recruited and randomly allocated to either the intervention group or the control group (in a 1:1 ratio). They will receive Wangbi granule or Wangbi placebo 12.0 g each time, three times a day for 12 weeks. The primary outcome is the disease activity score derivative for 28 joints (DAS28). Secondary outcomes are patient-reported outcomes, American College of Rheumatology 50% response criteria (ACR50), fatigue scale-14 (FS-14), visual analogue scale for pain (VAS), health assessment questionnaire disability index (HAQ-DI) and biomarkers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)., Expected Outcomes: The success of this study will provide strong evidence to confirm the efficacy and safety of Wangbi granule in the treatment of RA. Trial registration The trial has been registered in the ClinicalTrials Registry (NCT05540938, Date: 09/15/2022, https://clinicaltrials.gov/ct2/show/NCT05540938 )., (© 2023. The Author(s).)

Our previous phase Ib trial (NCT03222440) showed that radiotherapy plus the anti-PD-1 antibody camrelizumab is a safe and feasible first-line therapy for locally advanced esophageal squamous cell carcinoma. In this study, we divided peripheral CD8 T-cell differentiation subsets into 4 subpopulations (naive T cells, central memory T cells, effector memory T cells, and CD45RA+ effector memory T cells). We then investigated the influence of radiotherapy plus camrelizumab therapy on the proportions of the 4 subsets and their PD-1, TIGIT, and CTLA-4 expression as well as their proliferative activity and compared the effects with those of concurrent chemoradiotherapy. Nineteen and 15 patients with esophageal squamous cell carcinoma who received radiotherapy plus camrelizumab therapy and concurrent chemoradiotherapy, respectively, were enrolled in this study. We isolated peripheral blood mononuclear cells from these patients before treatment and longitudinally after the delivery of 40 Gy radiotherapy. Flow cytometry was conducted to detect peripheral CD8 T-cell subsets and PD-1, TIGIT, CTLA-4, and Ki67 expression levels in patients with esophageal squamous cell carcinoma. We found that radiotherapy plus camrelizumab therapy did not change the proportions of the 4 subsets or the expression of CTLA-4, but this therapy decreased PD-1 expression by the 4 subsets and TIGIT expression by effector memory T cells, as well as significantly enhanced the proliferative activity of CD8 T cells, whereas concurrent chemoradiotherapy produced different effects. In addition, we further identified peripheral biomarkers that potentially predict the outcome of radiotherapy plus camrelizumab therapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Body size judgements are frequently biased, or inaccurate, and these errors are further exaggerated for individuals with eating disorders. Within the eating disorder literature, it has been suggested that exaggerated errors in body size judgements are due to difficulties with integration. Across two experiments, we developed a novel integration task, named the Ebbinghaus Illusion for Bodies in Virtual Reality (VR), to assess whether nearby bodies influence the perceived size of a single body. VR was used to simulate the appearance of a small crowd around a central target body., Method and Results: In Experiment 1 ( N  = 412), participants were required to judge the size of a central female target within a crowd. Experiment 1 revealed an Ebbinghaus Illusion, in which a central female appeared larger when surrounded by small distractors, but comparatively smaller when surrounded by large distractors. In other words, the findings of Experiment 1 demonstrate that surrounding crowd information is integrated when judging an individual's body size; a novel measure of spatial integration (i.e., an Ebbinghaus Illusion for Bodies in VR). In Experiment 2 ( N  = 96), female participants were selected based on high ( n  = 43) and low ( n  = 53) eating disorder symptomatology. We examined whether the magnitude of this illusion would differ amongst those with elevated versus low eating disorder symptomatology, in accordance with weak central coherence theory, with the high symptomatology group displaying less spatial integration relative to the low group. The results of Experiment 2 similarly found an Ebbinghaus Illusion for Bodies in VR. However, illusion magnitude did not vary across high and low symptomatology groups., Discussion: Overall, these findings demonstrate that surrounding crowd information is integrated when judging individual body size; however, those with elevated eating disorder symptomatology did not show any integration deficit on this broader measure of spatial integration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Turnbull, Lego, Kennedy, Alexi, Li, Engel, Mann, Bayliss, Farrell and Bell.)

Background: Associations of depressive and anxiety symptoms with non-suicidal self-injury (NSSI) and suicide attempt (SA) are not well understood. We aimed to examine these associations among Chinese adolescents, and whether any potential association is mediated through sleep quality., Methods: We conducted a cross-sectional study among 1,771 (994 boys [56.1%] and 777 girls [43.9%], mean [SD] age was 12.9 [0.6] years) adolescents who participated in the baseline survey of the Chinese Adolescent Health Growth Cohort (CAHGC) study. Depressive symptoms, anxiety symptoms, NSSI, SA and sleep quality were measured by validated questionnaire. Logistic regression models were employed to estimate the associations of depression and anxiety with NSSI and SA. Mediation analyses were conducted to explore the mediate effect of sleep quality., Results: The 12-month prevalence of NSSI and SA was 17.1 and 8.3%, respectively. Depressive and anxiety symptoms were significantly associated with NSSI (the adjusted odds ratio [aOR] was 1.89 [95% CI 1.34-2.65] for depressive symptoms and 2.84 [95% CI 2.05-3.94] for anxiety symptoms) and SA (the aOR was 3.20 [95% CI 2.03-5.05] for depressive symptoms and 2.98 [95% CI 1.84-4.84] for anxiety symptoms). No significant gender differences were found in the associations. The mediation proportion of sleep quality on the association of depressive and anxiety symptoms with NSSI, as well as depressive and anxiety symptoms with SA were 21.1, 13.9, 13.6, and 14.7, respectively., Conclusion: Independent associations of depressive and anxiety symptoms with NSSI and SA were observed in Chinese adolescents, and there were no significant gender differences in the associations. Moreover, these associations were partially mediated through sleep quality. Targeted interventions for adolescents' NSSI and SA should focus on those who have depressive and anxiety symptoms, and poor sleep quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiao, Guo, Zhang, Li, Xie, Ma, Chen, Yu and Tang.)

Research has shown that body size judgements are frequently biased, or inaccurate. Critically, judgement biases are further exaggerated for individuals with eating disorders, a finding that has been attributed to difficulties integrating body features into a perceptual whole. However, current understanding of which body features are integrated when judging body size is lacking. In this study, we examine whether individuals integrate three-dimensional (3D) cues to body volume when making body size judgements. Computer-generated body stimuli were presented in a 3D Virtual Reality environment. Participants ( N  = 412) were randomly assigned to one of the two conditions: in one condition, the to-be-judged body was displayed binocularly (containing 3D cues to body volume); in the other, bodies were presented monocularly (two-dimensional [2D] cues only). Across 150 trials, participants were required to make a body size judgement of a target female body from a third-person point of view using an unmarked visual analogue scale (VAS). It was found that 3D cues significantly influenced body size judgements. Namely, thin 3D bodies were judged smaller , and overweight 3D bodies were judged larger , than their 2D counterpart. Furthermore, to reconcile these effects, we present evidence that the two perceptual biases, regression to the mean and serial dependence, were reduced by the additional 3D feature information. Our findings increase our understanding of how body size is perceptually encoded and creates testable predictions for clinical populations exhibiting integration difficulties.

Objective: The systematic immune status of cancer patients undergoing immunotherapy is little known. We prospectively identified the function and differentiation traits of peripheral CD8 + T cells based on our phase 1b clinical trial (NCT03222440) of radiotherapy combined with camrelizumab in patients with locally advanced esophageal squamous cell carcinoma (ESCC) and compared it with concurrent chemoradiotherapy (CCRT)., Methods: 19 and 18 patients were included in the cohort of radiotherapy plus camrelizumab and cohort of CCRT treatment. By using flow cytometry, we evaluated the expression levels of PD-1, Eomes, T-bet and IFN-γ (function), CD38 and HLA-DR (activation), and differentiation subsets classified according to the expression levels of CD45RA and CD62L in peripheral CD8 + T cells before and during treatment., Results: Effective binding of anti-PD-1 antibody camrelizumab with PD-1 on CD8 + T cells was detected during treatment. Both two treatments elevated the expression levels of activation molecules CD38 and HLA-DR on CD8 + T cells. PD-1 + CD8 + T cells had more activation features than PD-1 - CD8 + T cells in two groups and the treatments did not alter these differences. The two treatments activated both PD-1 + and PD-1 - CD8 + T cells. PD-1 + CD8 + T cells had less Naïve and TEMRA but more Tcm and Tem than PD-1 - CD8 + T cells in two groups and both two treatments changed the ratio of memory T cells in PD-1 + and PD-1 - cells. RT plus camrelizumab treatment reduced Naïve T cells and TEMRA subsets both in PD-1 + and PD-1 - CD8 + T cells while elevated Tcm subset in PD-1 + CD8 + T cells and Tem subset in PD-1 - CD8 + T cells. CCRT elevated Tcm subset and reduced TEMRA subset in PD-1 - CD8 + T cells while did not change any subset in PD-1 + CD8 + T cells. Furthermore, patients undergoing radiotherapy plus immunotherapy were found to obtain better prognosis than those receiving CCRT., Conclusions: This study identified the dynamic changes of systematic immune status of patients undergoing treatment. The two treatments had similar activation effects on peripheral CD8 + T cells with different PD-1 properties but had different effects on their differentiation status. These results provided potential clues to the reasons underlying the difference in prognosis of the two treatments., Competing Interests: Author JZ is employed by Jiangsu Hengrui Pharmaceuticals Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wei, Li, Guo, Ma, Li, Wei, Han, Zhang, Chen, Yan, Zhou, Pang, Wang and Zhang.)

Purpose: We aim to explore whether the gross volume of metastatic lymph nodes (GTVnd) and the gross volume of primary tumor (GTVp) could be prognostic factors for esophageal squamous cell carcinoma (ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT)., Methods: We retrospectively analyzed 252 ESCC patients treated with dCCRT in the era of intensity-modulated radiation therapy (IMRT) at our institution. The cut-off value for the GTVnd derived from the restricted cubic splines (RCS) was determined. Univariate and multivariate Cox proportional hazard models were performed to determine the association between GTVnd and prognosis. we performed recursive partitioning analysis (RPA) method using GTVnd to develop a new risk stratification (TGTVndM). Moreover, the linear trend χ2, likelihood ratio χ2, and akaike information criterion (AIC) were used to determine the prognostic value between the TNM and TGTVndM staging systems., Results: The five-year overall survival (OS) rate was 30.6%, with a median follow-up of 38 months. The cut-off value of GTVnd determined by the RCS was 4.35 cm 3 . GTVnd≥4.35 cm 3 was an independent and significant negative prognostic factor for OS (HR=1.949, P<0.001), progression free survival (PFS) (HR=1.425, P=0.048), and distance metastasis free survival (DMFS) (HR=2.548, P=0.001). In multivariable analysis, gender, clinical T stage, and GTVnd were independently associated with OS. RPA segregated patients into 3 prognostic groups: high risk (T1-4 GTVnd≥4.35, n=126, III stage), intermediate risk (T4 GTVnd<4.35,n=38,II stage), and low risk(T1-3GTVnd<4.35, n=88, I stage). The 5-year OS(P<0.001), PFS (P=0.002), and DMFS (P=0.001) were significantly worse in high-risk group in comparison with the intermediate and low risk groups. Compared with the TNM staging system, the clinical T stage combined with GTVnd (TGTVndM) had a higher linear trend χ2 (26.38 versus 25.77), higher likelihood ratio χ2 (24.39 versus 20.69), and lower AIC (1255.07 versus 1260.06)., Conclusions: GTVnd may serve as a good prognostic factor in predicting distant metastasis and death for ESCC patients treated with dCCRT. The TGTVndM staging system demonstrated superior accuracy for predicting OS and could serve as a more effective prognostic guidance for unresectable ESCC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Li, Huang, Guo, Zhang, Zhang, Pang and Wang.)

Background and Purpose: To evaluate the efficiency and safety of immunotherapy combined with or without radiotherapy (RT) for metastatic or recurrent esophageal squamous cell carcinoma (ESCC)., Methods: We retrospectively reviewed data of 127 patients with metastatic or recurrent ESCC, who received immunotherapy with or without RT at Tianjin Medical University Cancer Institute between 2017 and 2021., Results: The median follow-up time was 15.7 months (95 % confidence interval (CI): 12.42-18.99). The median PFS of the RT and NRT groups was 5.45 months (95 % CI: 2.89-8.28) and 4.60 months (95 % CI: 3.75-7.06), respectively ( P  = 0.660). The median OS was 11.9 (95 % CI: 8.61-19.2) and 10.3 (95 % CI: 7.56-15.8) months, respectively ( P  = 0.890). The median PFS of locoregional recurrence patients in the RT and NRT groups was 11.27 months (95 % CI: 2.45-20.09) and 4.17 months (95 % CI: 2.64-5.71), respectively ( P  = 0.081). The median OS of locoregional recurrent patients in the RT and NRT groups was 19.48 months (95 % CI: 8.37-30.60) and 7.69 months (95 % CI: 3.45-11.93), respectively ( P  = 0.026). 64 % of patients in the RT group and 30 % of patients in the NRT group experienced an improvement in dysphagia ( P  = 0.033). No significant increase in treatment-related toxicity was observed in the RT group compared with the NRT group, except for some hematological complications., Conclusions: Locoregional recurrent patients gained survival benefits from immunotherapy combined with RT. The combination of immunotherapy and RT was safe in metastatic/recurrent ESCC patients. RT for the esophagus leads to the improvement of dysphagia compared to immunotherapy alone., 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., (© 2022 The Authors.)

Background: PD-1/PD-L1 tumor immunotherapy shows effective anticancer in treatment of solid tumors, so PEI lipid nanoparticles (PEI-LNP)/siRNA complex (EPV-PEI-LNP-SiRNA) with the therapeutic function of PD-L1-siRNA and EGFR short peptide/PD-L1 double immune-enhancing function were constructed for the prevention and treatment of EGFR-positive lung cancer in this study., Method: In this study, PEI lipid nanoparticles (PEI-LNP)/siRNA complex (EPV-PEI-LNP-siRNA) with the therapeutic function of PD-L1-siRNA and EGFR short peptide/PD-L1 double immune-enhancing function were constructed for the prevention and treatment of EGFR-positive lung cancer and functional evaluation was conducted., Results: On the basis of the construction of the composite nano-drug delivery system, the binding capacity, cytotoxicity, apoptosis and uptake capacity of siRNA and EPV-PEI-LNP were tested in vitro, and the downregulation effect of PD-L1 on A549 cancer cells and the cytokine levels of cocultured T cells were tested. Lipid nanoparticles delivered siRNA and EGFR short peptide vaccine to non-small cell lung cancer (NSCLC), increasing tumor invasion and activation of CD8 + T cells. Combination therapy is superior to single target therapy., Conclusion: Our constructed lipid nanoparticles of tumor targeted therapy gene siRNA combination had the ability to target cells in vitro and downregulate the expression of PD-L1, realizing the tumor-specific expression of immune-stimulating cytokines, which is a highly efficient and safe targeted therapy nano-vaccine., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

The emergence and spread of bacterial resistance to antibiotics has developed into one of the most challenging threats to public health. Antibiotic susceptibility tests (ASTs) for bacterial infections are now essential, because they provide guidance for physicians in the selection of antibiotics, to which bacteria will respond. Most current AST methods require long periods of time, because of bacterial growth and incubation, leading to a prolonged and overuse of broad-spectrum antibiotics. Thus, there is a growing demand for methods and technologies that enable rapid antibiotic susceptibility assessment. Due to advantages related to cost-effectiveness, rapid response time and high sensitivity, electrochemical detection methods are promising analytical tools that can successfully quantify antibiotic uptake and retention in clinically relevant bacterial strains. This study presents the electroanalytical quantification of tobramycin (TOB) retention in susceptible and resistant bacterial strains of Pseudomonas aeruginosa . The electrochemical behavior of TOB was characterized by voltammetry, identifying redox potentials, the current dependence on pH conditions, and the detection limit at unmodified glassy carbon electrodes. The presented methodology was able to distinguish between susceptible and resistant bacterial strains, and is also capable of identifying varying degrees of resistance against TOB. The presented approach detects the immediate interaction of bacteria with an antibiotic, without the need of complex and cost-intense equipment related to genomic testing methods.

After placing an active capping material on surface sediments, the capping layer will be buried by the newly formed sediment. In this research, the influence of sediment burial depth on the performance of iron/aluminum co-modified calcite (FeAlCAL) to suppress sedimentary phosphorus (P) release into overlaying water (OL-water) was studied. Furthermore, in order to find out the strategy for overcoming the negative effect of sediment burial, the efficiencies and mechanisms of three different FeAlCAL treatments (one-time FeAlCAL capping with 3 cm sediment burial, multiple FeAlCAL capping with 1 cm sediment burial, and amendment of top 3 cm sediment with FeAlCAL) in the inhibition of sediment P release were contrastively studied. The results showed that with the increase of sediment burial depth, the efficiency of FeAlCAL to block the release of sediment P into OL-water gradually decreased until the FeAlCAL lost the ability to hinder sediment-P release. In contrast to the one-time FeAlCAL capping in the presence of 3 cm sediment burial, the multiple FeAlCAL capping in the presence of 1 cm sediment burial and amendment of top 3 cm sediment with FeAlCAL both effectively prevented the release of P from sediment into OL-water. All results of this work suggest that although sediment burial can negatively affect the ability of FeAlCAL in the inhibition of sediment P release into OL-water and the negative effect becomes stronger as the sediment burial depth increases, the transformation of the application mode of FeAlCAL from one-time capping to multiple capping or from capping to amendment can overcome the negative influence of sediment burial., 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.)

Introduction: Visual Analogue Scale (VAS) and the pain subscale of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) are commonly used measuring tools of osteoarthritis (OA) pain., Objectives: The objective of this cross-sectional study was to explore the associations between single-question VAS pain and the weight-bearing and non-weight-bearing domains of WOMAC pain., Methods: Data from 2093 patients with OA participating in 2 phase 3 clinical trials were included for post hoc analyses. Univariate Pearson correlations and comparison of r values were made using z statistics obtained using the Fisher r to z test for all items of the VAS pain scale, the WOMAC pain subscale, the weight-bearing and non-weight-bearing constructs of WOMAC pain subscale, and by subgroups of WOMAC pain quintiles and Kellgren-Lawrence grades ., Results: The correlations between VAS pain and WOMAC pain were significant ( r = 0.67, P < 0.001) with a slope of 0.57 (95% confidence interval [CI]: 0.54-0.61). A similar correlation was found for weight-bearing pain ( r = 0.68, P < 0.001, slope: 0.62 (95% CI: 0.59-0.65) but significantly lower for non-weight-bearing pain ( r = 0.55, P < 0.001, slope: 0.49 (95% CI: 0.46-0.52). The degree of disagreement between the 2 instruments seemed to be lesser in the extreme ends of the scales, and the observed association between Kellgren-Lawrence grade and disagreement between VAS and WOMAC was driven by non-weight-bearing pain., Conclusion: In conclusion, VAS pain and WOMAC pain subscale correlation was found to be moderate and the VAS pain scale correlated more accurately with the WOMAC pain weight-bearing questions. This constitutes novel insight into patient with OA pain reporting., Competing Interests: J.J. Bjerre-Bastos, C.P. Miller, Y. Li, J.R. Andersen, and A.R. Bihlet are full-time employees of NBCD A/S. Y. Li, J.R. Andersen, and A.R. Bihlet are shareholders of NBCD A/S. M. Karsdal is a shareholder of Nordic Bioscience A/S.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Metabolic disorders induced by arsenic exposure have attracted great public concern. However, it remains unclear whether hypothalamus-based central regulation mechanisms are involved in this process. Here, we exposed mice to 100 μg/L arsenic in drinking water and established a chronic arsenic exposure model. Our study revealed that chronic arsenic exposure caused metabolic disorders in mice including impaired glucose metabolism and decreased energy expenditure. Arsenic exposure also impaired glucose sensing and the activation of proopiomelanocortin (POMC) neurons in the hypothalamus. In particular, arsenic exposure damaged the plasticity of hypothalamic astrocytic process. Further research revealed that arsenic exposure inhibited the expression of sex-determining region Y-Box 2 (SOX2), which decreased the expression level of insulin receptors (INSRs) and the phosphorylation of AKT. The conditional deletion of astrocytic SOX2 exacerbated arsenic-induced effects on metabolic disorders, the impairment of hypothalamic astrocytic processes, and the inhibition of INSR/AKT signaling. Furthermore, the arsenic-induced impairment of astrocytic processes and inhibitory effects on INSR/AKT signaling were reversed by SOX2 overexpression in primary hypothalamic astrocytes. Together, we demonstrated here that chronic arsenic exposure caused metabolic disorders by impairing SOX2-modulated hypothalamic astrocytic process plasticity in mice. Our study provides evidence of novel central regulatory mechanisms underlying arsenic-induced metabolic disorders and emphasizes the crucial role of SOX2 in regulating the process plasticity of adult astrocytes., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Liver fibrosis is a necessary process for liver disease. Recent studies have reported that the enterohepatic circulation of bile acid plays a vital role in developing liver fibrosis. The Antarctic krill peptide (AKP) has been proved to have a variety of activities such as antioxidant and anti-inflammatory, but any possible influence on liver fibrosis remains unclear. In the current study, the liver fibrosis mice were intraperitoneal injection of carbon tetrachloride (2.5%, 10 mL kg -1 ) and oral administration AKP (400 mg kg -1 ) for 30 days. The results showed that the AKP supplement decreased the serum ALT and AST levels, reduced the content of liver TNF-α and Collagen I, and improved liver inflammation and fibrosis, which was also confirmed by H&E and Masson staining. Bile acid is an important metabolite for the gut microbiota. We found that the AKP supplement alleviated the gut microbiota dysbiosis remarkably, as indicated by increased species richness and diversity, and decreased overgrowth of genera Bifidobacterium, Lactobacillus, Bacteroides, Clostridiales and Fusicatenibacter. Furthermore, AKP mediated gut microbiota improvement decreased the intestinal bile salt hydrolase and 7α-dehydroxylation activities, resulting in the decrease of secondary bile acid taurodeoxycholic acid (TDCA) and taurolithocholic acid (TLCA) concentrations. Mechanistically, AKP inhibited NLRP3 signal by downregulating the secondary bile acid, decreased cleaved Caspase-1 expression to suppress IL-1β-mediated hepatic stellate cell activation. This study reports for the first time that AKP improved liver fibrosis via improving the gut microbiota mediated bile acid-NLRP3 signaling, which might provide new ideas and evidence for Antarctic krill's high-value utilization.