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Background: Sarcomatoid carcinoma (SCA) of the jejunum is a rare and aggressive neoplasm affecting the smooth muscle cells of the jejunum. This study presents a recent case of jejunal SCA, detailing its diagnosis and treatment, thereby providing a reference for clinical practice., Case Summary: A 65-year-old male presented to Yichang Central People's Hospital with a chief complaint of hemorrhoids. A computed tomography (CT) scan incidentally revealed multiple abnormal signals in the liver. Subsequent positron emission tomography/CT at Wuhan Union Hospital indicated malignant tumor progression, with a primary duodenal tumor and multiple metastases in the upper left abdomen. Intraoperatively, a large tumor was identified on the omentum. Histopathological and immunohistochemical analyses of the resected specimen confirmed the diagnosis of jejunal SCA. The patient received a combination therapy of sintilimab, nanoparticle albumin-bound paclitaxel, and anlotinib. Follow-up imaging demonstrated significant reduction of hepatic and peritoneal lesions. The patient has remained stable for over one year postoperatively., Conclusion: This case suggests that chemotherapy, immunotherapy, plus targeted therapy may represent an optimal treatment for intestinal SCA, meriting further investigation., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Various pretreatments are commonly adopted to facilitate dissolved organic matter (DOM) release from waste activated sludge (WAS) for high-valued volatile fatty acids (VFAs) promotion, while the interplay impact of DOM dynamics transformation on microbial population and metabolic function traits is poorly understood. This work constructed "DOM-microorganisms-metabolism-VFAs" symbiotic ecologic networks to disclose how DOM dynamics variation intricately interacts with bacterial community networks, assembly processes, and microbial traits during WAS fermentation. The distribution of DOM was altered by different pretreatments, triggering the release of easily biodegradable compounds (O/C ratio > 0.3) and protein-like substance. This alteration greatly improved the substrates biodegradability (higher biological index) and upregulated microbial metabolism capacity (e.g., hydrolysis and fatty acid synthesis). In turn, microbial activity modifications augment substance metabolism level and expedite the conversion of highly reactive compounds (proteins-like DOM) to VFAs, leading to 1.6-4.2 fold rise in VFAs generation. Strong correlations were found between proteins-like DOM and topological properties of DOM-bacteria associations, suggesting that high DOM availability leads to more intricate ecological networks. A change in the way communities assemble, shifting from stronger uniform selection in pH10 and USp reactors to increased randomness in heat reactor, was linked to DOM composition alterations. The ecologic networks further revealed metabolic synergy between hydrolytic-acidogenic bacteria (e.g., Bacteroidota and Firmicutes) and biodegradable DOM (e.g., proteins and amino sugars) leading to higher VFAs generation. This study provides a deeper knowledge of the inherent connections between DOM and microbial traits for efficient VFAs biosynthesis during WAS anaerobic fermentation, offering valuable insights for effective WAS pretreatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Various exogenous contaminants typically coexist in waste activated sludge (WAS), and the long-term impacts of these co-occurring contaminants on WAS anaerobic fermentation and associated mechanisms remain largely unknown. This study reveals that the co-occurrence of surfactants and nanoparticles (NPs, i.e., Fe 2 O 3 and CeO 2 , frequently detected in sludge) exhibited time-dependent impacts on the volatile fatty acids (VFAs) biosynthesis. Surfactants triggered WAS decomposition and enhanced NPs dispersion, leading to increased exposure of functional anaerobes to NPs toxicity, negatively affecting them. Consequently, key fermentation processes, acidogenic bacterial abundance, and metabolic functions were inhibited in co-occurrence reactors compared to those containing only surfactants in the early stage (before 56 d). Surprisingly, the fermentation systems containing surfactants collapsed subsequently, with VFAs yield at 72 d decreasing by 48.59-71.27 % compared to 56 d. The keystone microbes (i.e., Acidobacteria (16 d) vs Patescibacteria (56 d)) were reshaped, and metabolic traits (i.e., proB involved in intracellular metabolism) were downregulated by 0.05-78.02 % due to reduced microbial adaptive capacity (i.e., quorum sensing (QS)). Partial least squares path modeling (PLS-PM) analysis suggests that the microbial community was the predominant factor influencing VFAs generation. This study provides new insights into the long-term effects of co-contaminants on the biological treatment of WAS., 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.)

Microneedles are a novel drug delivery system that offers advantages such as safety, painlessness, minimally invasive administration, simplicity of use, and controllable drug delivery. As a type of polymer microneedle with a three-dimensional network structure, hydrogel microneedles (HMNs) possess excellent biocompatibility and biodegradability and encapsulate various therapeutic drugs while maintaining drug activity, thus attracting significant attention. Recently, they have been widely employed to promote wound healing and have demonstrated favorable therapeutic effects. Although there are reviews about HMNs, few of them focus on wound management. Herein, we present a comprehensive overview of the design and preparation methods of HMNs, with a particular emphasis on their application status in wound healing, including acute wound healing, infected wound healing, diabetic wound healing, and scarless wound healing. Finally, we examine the advantages and limitations of HMNs in wound management and provide suggestions for future research directions.

A facile synthetic method for direct C(sp 2 )-H bond trifluoromethylation of 3-methylene-isoindolin-1-ones under visible-light-induced metal-free conditions is presented. This protocol features mild reaction conditions, broad substrate scope and excellent functional group tolerance, resulting in a range of structurally diverse trifluoromethylated products in good to excellent yields.

Although catenated cages have been widely constructed due to their unique and elegant topological structures, cyclic catenanes formed by the connection of multiple catenane units have been rarely reported. Herein, based on the orthogonal metal-coordination-driven self-assembly, we prepare a series of heterometallic [2]catenanes and cyclic bis[2]catenanes, whose structures are clearly evidenced by single-crystal X-ray analysis. Owing to the multiple positively charged nature, as well as the potential synergistic effect of the Cu(I) and Pt(II) metal ions, the cyclic bis[2]catenanes display broad-spectrum antibacterial activity. This work not only provides an efficient strategy for the construction of heterometallic [2]catenanes and cyclic bis[2]catenanes but also explores their applications as superior antibacterial agents, which will promote the construction of advanced supramolecular structures for biomedical applications., (© 2024 Wiley-VCH GmbH.)

Numerous neuroimaging studies have identified significant individual variability in intertemporal choice, often attributed to three neural mechanisms: (1) increased reward circuit activity, (2) decreased cognitive control, and (3) prospection ability. These mechanisms that explain impulsivity, however, have been primarily studied in the gain domain. This study extends this investigation to the loss domain. We employed a hierarchical Bayesian drift-diffusion model (DDM) and the inter-subject representational similarity approach (IS-RSA) to investigate the potential computational neural substrates underlying impulsivity in loss domain across two experiments (n = 155). These experiments utilized a revised intertemporal task that independently manipulated the amounts of immediate and delayed-loss options. Behavioral results demonstrated positive correlations between the drift rate, measured by the DDM, and the impulsivity index K in Exp. 1 (n = 97) and were replicated in Exp. 2 (n = 58). Imaging analyses further revealed that the drift rate significantly mediated the relations between brain properties (e.g., prefrontal cortex activations and gray matter volume in the orbitofrontal cortex and precuneus) and K in Exp. 1. IS-RSA analyses indicated that variability in the drift rate also mediated the associations between inter-subject variations in activation patterns and individual differences in K. These findings suggest that individuals with similar impulsivity levels are likely to exhibit similar value processing patterns, providing a potential explanation for individual differences in impulsivity within a loss framework., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Objectives: Remnant cholesterol (RC) is thought to be an important pathogenic risk factor for atherosclerosis, however, the relationship between RC and acute ischemic stroke (AIS) is still unclear. This study aimed to determine whether fasting blood RC level is an independent risk factor for AIS., Materials and Methods: A retrospective analysis was performed on 650 patients with AIS and 598 healthy controls during the same time period. The association between RC and AIS was investigated using binary logistic regression, and the relationship between RC and AIS risk was demonstrated using Restricted Cubic Splines (RCS)., Results: RC was significantly higher in the AIS group compared with control group, and was an independent risk factor for AIS when the covariates were not adjusted;After adjusting some covariates, RC was still an independent risk factor for AIS. The RCS analysis found the risk was non-linear: when RC concentration was less than 0.69 mol/L, the risk of AIS increased with the elevation of RC, and when RC concentration was more than or equal to 0.69 mol/L, the risk of AIS was insignificant with the elevation of RC. Correlation analysis revealed that RC was associated with diabetes and fasting glucose. Further analysis revealed that the incidence of AIS in diabetic patients increased significantly with the increase of RC, and RCS analysis revealed that the risk of AIS in diabetic patients increased with the increase of RC when RC was more than 1.15 mol/L., Conclusions: This study confirms RC as an independent risk factor for AIS, which highlights a distinct non-linear association between RC levels and AIS risk. These findings suggest the need for targeted AIS risk assessment strategies, especially in diabetic patients, and underscore the relevance of RC as a biomarker in AIS risk stratification., Competing Interests: Declaration of competing interest Authors declared no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: This research focused on meticulously tracking and identifying adverse reactions associated with leuprorelin, a drug prescribed for conditions such as prostate cancer, endometriosis, uterine fibroids, and early-onset puberty. The main objective was to enhance patient safety and offer informed guidance on the appropriate use of this treatment., Methods: From the first quarter of 2004 to the fourth quarter of 2023, a comprehensive analysis was conducted on a significant number of adverse event reports (AERs) from the FDA Adverse Event Reporting System (FAERS) database. Data mining with dismutation analysis was conducted to quantify signals associated with adverse events (AEs) related to leuprorelin, utilizing powerful algorithms such as ROR, PRR, BCPNN, and EBGM., Results: A total of 102 positive reaction terms (PT) spanning 24 System Organ Classes (SOCs) were identified from an analysis of 60,709 reports associated with leuprorelin use. Notably, several previously unrecognized adverse reactions were uncovered, including Artificial Menopause, Ovarian Adhesion, Follicular Cystitis, Intercepted product preparation error, among others. These findings underscore the importance of exercising additional vigilance regarding the potential adverse effects of leuprorelin, such as Abscess Sterile, Injection site granuloma, Intercepted medication error, and Bulbospinal muscular atrophy congenital., Conclusions: This research has successfully uncovered new and unforeseen signals associated with adverse drug reactions (ADRs) following leuprorelin administration. The study provides valuable insights into the intricate connection between ADRs and leuprorelin usage. The results underscore the crucial significance of continuous surveillance and meticulous monitoring to promptly identify and manage AEs, ultimately enhancing patient safety and well-being while undergoing leuprorelin therapy., 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Postoperative adhesion is a common complication after abdominal surgery, but current clinical products have unsatisfactory therapeutic effects. Here, we present a hydrogel patch formed in a single step through dialysis. The exchange of DMSO into water facilitates hydrophobic aggregate in situ formation and the formation of hydrogen bonds within the hydrogel. Thanks to the optimized component ratio and precise structural design. The hydrogel patch has soft-tissue-like mechanical characteristics, including high strength, high toughness, low modulus similar to the abdominal wall, good fatigue resistance, and fast self-recovery properties. The nonswellable hydrogel patch retains over 80% of its original mechanical properties after 7 days of immersion in physiological saline, with a maximum swelling ratio of 5.6%. Moreover, the hydrophobic biomultifunctionality of benzyl isothiocyanate can self-assemble onto the hydrogel patch during the sol-gel transition process, enabling it to remodel the inflammatory microenvironment through synergistic antibacterial, antioxidant, and anti-inflammatory effects. The hydrogel patch prevents postsurgical adhesion in a rat sidewall defect-cecum abrasion model and outperforms the leading commercial Interceed. It holds promising potential for clinical translation, considering that FDA-approved raw materials (PVA and gelatin) form the backbone of this effective hydrogel patch.

Immunological dysregulation plays a fundamental role in the inflammatory aspects of endometriosis. Circulating blood leukocytes, one of the most abundant immune cell populations in the human body, have been shown diagnostic significance in some diseases. Nevertheless, the association between peripheral blood leukocyte counts and endometriosis remains unexplored to date. We analysed two targeted study cohorts: a tertiary centre cohort (Endometriosis at Oxford University [ENDOX] study, 325 cases/177 controls) and a large-scale population study (UK Biobank [UKBB], 1537 cases/6331 controls). In both datasets, peripheral venous blood sample results were retrieved and counts of leukocyte subpopulations, including neutrophils, lymphocytes, monocytes, eosinophils and basophils analysed. Logistic regression models were used to investigate the association of leukocyte subtype alterations with endometriosis status, adjusting for confounding factors. We demonstrate that higher blood basophil level is associated with increased odds of endometriosis. This association was first discovered in the ENDOX cohort (basophils >0.04 x10^9/L: OR 1.65 [95%CI:1.06-2.57], P trend = 0.025) and replicated in the UKBB dataset (basophils >0.04 x10^9/L: OR 1.26 [95%CI:1.09-1.45], P trend = 0.001). Notably, women with basophil counts in the upper tercile had significantly increased odds of having stage III/IV endometriosis (ENDOX study: OR = 2.30, 95% CI [1.25 to 4.22], P trend = 0.007; UKBB study (OR = 1.40, 95% CI [1.07 to 1.85], P trend = 0.015). None of the other leukocyte subtypes showed an association. Our findings suggest an association between inflammatory responses and the pathogenesis of endometriosis; future studies are warranted to investigate whether the association is causal.

The treatment of infected wounds poses a formidable challenge in clinical practice due to the detrimental effects of uncontrolled bacterial infection and excessive oxidative stress, resulting in prolonged inflammation and impaired wound healing. In this study, we presented a MXene@TiO 2 (MT) nanosheets loaded composite hydrogel named as GA/OKGM/MT hydrogel, which was formed based on the Schiff base reaction between adipic dihydrazide modified gelatin (GA)and Oxidized Konjac Glucomannan (OKGM), as the wound dressing. During the hemostasis phase, the GA/OKGM/MT hydrogel demonstrated effective adherence to the skin, facilitating rapid hemostasis. In the subsequent inflammation phase, the GA/OKGM/MT hydrogel effectively eradicated bacteria through MXene@TiO 2 -induced photothermal therapy (PTT) and eliminated excessive reactive oxygen species (ROS), thereby facilitating the transition from the inflammation phase to the proliferation phase. During the proliferation phase, the combined application of GA/OKGM/MT hydrogel with electrical stimulation (ES) promoted fibroblast proliferation and migration, leading to accelerated collagen deposition and angiogenesis at the wound site. Overall, the comprehensive repair strategy based on the GA/OKGM/MT hydrogel demonstrated both safety and reliability. It expedited the progression through the hemostasis, inflammation, and proliferation phases of wound healing, showcasing significant potential for the treatment of infected wounds., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Regulating the microalgal initial adhesion in biofilm formation is a key approach to address the challenges of attached microalgae cultivation. As a type of phytohormone, Indole-3-acetic acid (IAA) can promote the growth and metabolism of microalgae. However, limited knowledge has been acquired of how IAA can change the initial adhesion of microalgae in biofilm formation. This study focused on investigating the initial adhesion of microalgae under different IAA concentrations exposure in biofilm formation. The results showed that IAA showed obvious hormesis-like effects on the initial adhesion ability of microalgae biofilm. Under exposure to the low concentration (0.1 mg/L) of IAA, the initial adhesion quantity of microalgae on the surface of the carrier reached the highest value of 7.2 g/m 2 . However, exposure to the excessively high concentration (10 mg/L) of IAA led to a decrease in the initial adhesion capability of microalgal biofilms. The enhanced adhesion of microalgal biofilms due to IAA was attributed to the upregulation of genes related to the Calvin Cycle, which promoted the synthesis of hydrophobic amino acids, leading to increased protein secretion and altering the surface electron donor characteristics of microalgal biofilms. This, in turn, reduced the energy barrier between the carriers and microalgae. The research findings would provide crucial support for the application of IAA in regulating the operation of microalgal biofilm systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy. Here, we report two perylene diimide-based metallacages that can form stable host-guest complexes with planar conjugated molecules including polycyclic aromatic hydrocarbons and photosensitizers (hypocrellin A). Such host-guest complexation not only prevents the aggregation of photosensitizers in aqueous environments, but also offers fluorescence resonance energy transfer (FRET) from the metallacage to the photosensitizers to further improve the singlet oxygen generation (Φ Δ  = 0.66). The complexes are further assembled with amphiphilic polymers, forming nanoparticles with improved stability for anticancer study. Both in vitro and in vivo studies indicate that the nanoparticles display excellent anticancer activities upon light irradiation, showing great potential for cancer photodynamic therapy. This study provides a straightforward and effective approach for enhancing the photosensitivity of conventional photosensitizers via host-guest complexation-based FRET, which will open a new avenue for host-guest chemistry-based supramolecular theranostics., (© 2024. The Author(s).)

Background: Cerebral small vessel disease (CSVD) includes vascular disorders characterized by heterogeneous pathomechanisms and different neuropathological clinical manifestations. Cognitive dysfunction in CSVD is associated with reductions in structural covariance networks (SCNs). A majority of research conducted on SCNs focused on group-level analysis. However, it is crucial to investigate the individualized variations in order to gain a better understanding of heterogeneous disorders such as CSVD. Therefore, this study aimed to utilize individualized differential structural covariance network (IDSCN) analysis to detect individualized structural covariance aberration., Methods: A total of 35 healthy controls and 33 CSVD patients with cognitive impairment participated in this investigation. Using the regional gray matter volume in their T1 images, the IDSCN was constructed for each participant. Finally, the differential structural covariance edges between the two groups were determined by comparing their IDSCN using paired-sample t-tests. On the basis of these differential edges, the two subtypes of cognitively impaired CSVD patients were identified., Results: The findings revealed that the differential structural covariance edges in CSVD patients with cognitive impairment showed a highly heterogeneous idistribution, with the edges primarily cross-distributed between the occipital lobe (specifically inferior occipital gyrus and cuneus), temporal lobe (specifically superior temporal gyrus), and the cerebellum. To varying degrees, the inferior frontal gyrus and the superior parietal gyrus were also distributed. Subsequently, a correlation analysis was performed between the resulting differential edges and the cognitive scale scores. A significant negative association was observed between the cognitive scores and the differential edges distributed in the inferior frontal gyrus and inferior occipital gyrus, the superior temporal gyrus and inferior occipital gyrus, and within the temporal lobe. Particularly in the cognitive domain of attention, the two subtypes separated by differential edges exhibited differences in cognitive scale scores [Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)]. The differential edges of the subtype 1, characterized by lower cognitive level, were mainly cross-distributed in the limbic lobe (specifically the cingulate gyrus and hippocampus), the parietal lobe (including the superior parietal gyrus and precuneus), and the cerebellum. In contrast, the differential edges of the subtype 2 with a relatively high level of cognition were distributed between the cuneus and the cerebellum., Conclusions: The differential structural covariance was investigated between the healthy controls and the CSVD patients with cognitive impairment, showing that differential structural covariance existed between the two groups. The edge distributions in certain parts of the brain, such as cerebellum and occipital and temporal lobes, verified this. Significant associations were seen between cognitive scale scores and some of those differential edges .The two subtypes that differed in both differential edges and cognitive levels were also identified. The differential edges of subtype 1 with relatively lower cognitive levels were more distributed in the cingulate gyrus, hippocampus, superior parietal gyrus, and precuneus. This could potentially offer significant benefits in terms of accurate diagnosis and targeted treatment of heterogeneous disorders such as CSVD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: RAS , BRAF , and mismatch repair (MMR)/microsatellite instability (MSI) are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer (CRC). However, their characteristics and influencing factors in Chinese patients have not been thoroughly described., Aim: To analyze the clinicopathological features of KRAS , NRAS , BRAF , and PIK3CA mutations and the DNA MMR status in CRC., Methods: We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital. MMR proteins were tested using immunohistochemical analysis, and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction. Microsatellite status was determined using an MSI detection kit. Statistical analyses were conducted using SPSS software and logistic regression., Results: The KRAS , NRAS , BRAF , and PIK3CA mutations were detected in 44.6%, 3.4%, 3.7%, and 3.9% of CRC patients, respectively. KRAS mutations were more likely to occur in patients with moderate-to-high differentiation. BRAF mutations were more likely to occur in patients with right-sided CRC, poorly differentiated, or no perineural invasion. Deficient MMR (dMMR) was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas. KRAS , NRAS , BRAF , and PIK3CA mutations were detected in 29.6%, 1.1%, 8.1%, and 22.3% of patients with dMMR, respectively. The dMMR was more likely to occur in patients with a family history of CRC, aged < 50 years, right-sided CRC, poorly differentiated histology, no perineural invasion, and with carcinoma in situ , stage I, or stage II tumors., Conclusion: This study analyzed the molecular profiles of KRAS , NRAS , BRAF , PIK3CA , and MMR/MSI in CRC, identifying key influencing factors, with implications for clinical management of CRC., Competing Interests: Conflict-of-interest statement: Xiao-Li Shi is currently employed by Geneis Beijing Co. Ltd. The authors declare that this research was conducted in the absence of potential conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The ureteral stent is an effective treatment for clinical ureteral stricture following urological surgery, and the functional coating of the stent could effectively inhibit bacterial colonization and other complications. The present review provides an analysis and description of the materials used in ureteral stents and their coatings. Emphasis is placed on the technological advancements of functional coatings, taking into consideration the characteristics of these materials and the properties of their active substances. Furthermore, recent advances in enhancing the therapeutic efficacy of functional coatings are also reviewed. It is anticipated that this article will serve as a valuable reference providing insights for future research development on new drug-loaded ureteral stents., 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.)

Ultrasonic extraction of Osmanthus fragrans was used for reducing Ag + to prepare AgNPs, which were further loaded on barley distiller's grains shell biochar. By supplementary of sodium alginate and tannic acid, composite gel beads were prepared. The physical properties of biochar-based AgNPs‑sodium alginate-tannic acid composite gel beads (C-Ag/SA/TA) were characterized. SEM, FTIR, and XRD showed that biochar-based AgNPs were compatible with sodium alginate-tannic acid. CAg greatly improved the dissolution, swelling, and expansion of gel beads. Through the analysis by the agar diffusion method, C-Ag/SA/TA gel beads had high antibacterial activity (inhibition zone: 22 mm against Escherichia coli and 20 mm against Staphylococcus aureus). It was observed that C-Ag/SA/TA composite gel beads had high antioxidant capacity and the free radical scavenging rate reached 89.0 %. The dye adsorption performance of gel beads was studied by establishing a kinetic model. The maximum adsorption capacities of C-Ag/SA/TA gel beads for methylene blue and Congo red were 166.57 and 318.06 mg/g, respectively. The removal rate of Cr(VI) reached 96.4 %. These results indicated that the prepared composite gel beads had a high adsorption capacity for dyes and metal ions. Overall, C-Ag/SA/TA composite gel beads were biocompatible and had potential applications in environmental pollution treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Frequent oil spills pose significant threats to ecosystems; therefore, strict requirements are needed for prompt remediation and reclamation of spilled oil. Influenced by the structure of coniferous trees and their water transport, this experiment used cellulose nanofiber (CNF), polyvinyl alcohol (PVA), and methyltrimethoxysilane (MTMS) to prepare radially centrosymmetric aerogels. By utilizing the in-situ polycondensation reaction of MTMS, CNF, and PVA were connected, and the hydrophobicity and mechanical properties of the aerogel were greatly enhanced. Furthermore, the introduction of graphene oxide (GO), enshrouded within the cross-linked network, engenders heightened photo-thermal effects. The resultant composite aerogel exhibits expeditious oil absorption under solar irradiation and radial layered channel architecture, significantly curtailing the crude oil absorption timeframe (achieving a maximum absorption capacity of 51.7 g/g). Moreover, it demonstrates superior performance in rapidly and repeatedly adsorbing highly viscous crude oil, surpassing existing literature. Notably, continuous absorption of high-viscosity crude oil is achieved by integrating the composite aerogel with a peristaltic pump. This study offers a novel approach to the absorption and retrieval of high-viscosity crude oil, broadening the potential application horizons of CNF-based aerogels within environmental remediation., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We described an 82-year-old man who was taken to our emergency department after being found unconscious. His electrocardiogram (ECG) showed ST-segment elevation in leads V4-V6 and cardiac troponin I (cTnI) was abnormally elevated. In addition to ECG and cTnI changes, this patient was combined with unconsciousness, high fever, abnormal liver function, acute renal failure, and rhabdomyolysis. The initial diagnosis was heat stroke, so cooling measures were initiated immediately, but a concurrent myocardial infarction was suspected. Meanwhile, emergency coronary angiography was performed, but no severe coronary stenosis or thrombosis was found. We first evaluated quantitative flow ratio (QFR) and coronary angiography-derived index of microvascular resistance (ca-IMR) in patients with heat stroke. Ca-IMR was 260 mmHg*s/m in the left circumflex artery, indicating the presence of coronary microvascular dysfunction (CMD). After several days of treatment, the patient recovered from multiple organ damage. Therefore, ECG and troponin results should be interpreted carefully in patients with high fever and coma during high temperature seasons., Competing Interests: Declaration of competing interest All authors declared no conflicts of interest., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

In this work, a new rapid and targeted method for screening α-glucosidase inhibitors from Hypericum beanii was developed and verified. Ten new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperlagarol A-J ( 1 - 10 ), and nine known PPAPs ( 11 - 19 ) were obtained from H. beanii . Their structures were identified by using comprehensive analyses involving mass spectrometry, ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and electron capture dissociation calculations. 1 and 2 are two new rare 2,3- seco -spirocyclic PPAPs, 3 and 4 are two novel 12,13- seco -spirocyclic PPAPs, 5 and 6 are two novel spirocyclic PPAPs, 7 and 8 are two new unusual spirocyclic PPAPs with complex bridged ring systems, and 9 and 10 are two novel nonspirocyclic PPAPs. α-GC inhibitory activities of all isolated compounds were tested. Most of them displayed inhibitory activities against α-glucosidase, with the IC 50 values ranging from 6.85 ± 0.65 to 112.5 ± 9.03 μM. Moreover, the inhibitory type and mechanism of the active compounds were further analyzed using kinetic studies and molecular docking.

Study Question: Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)?, Summary Answer: PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression., What Is Known Already: High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood., Study Design, Size, Duration: Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated., Participants/materials, Setting, Methods: The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches., Main Results and the Role of Chance: Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice., Large Scale Data: N/A., Limitations, Reasons for Caution: Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls., Wider Implications of the Findings: Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus., Study Funding/competing Interest(s): This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: The diagnosis of unexplained infertility presents a dilemma as it signifies both uncertainty about the cause of infertility and the potential for natural conception. Immediate treatment of all would result in overtreatment. Prediction models estimating the likelihood of natural conception and subsequent live birth can guide treatment decisions., Objective: To evaluate if in couples with unexplained infertility, prediction models are effective in guiding treatment decisions., Evidence Review: This review examines 25 studies that assess prediction models for natural conception in couples with unexplained infertility in terms of derivation, validation, and impact analysis., Findings: The largest prediction models have been integrated in the synthesis models of Hunault, which includes female age and infertility duration, having been pregnant before and motile sperm percentage. Despite its limited discriminative capacity, this model demonstrates excellent calibration. Importantly, the impact of the Hunault model has been evaluated in randomized clinical trials, and shows that in couples with unexplained infertility and 12-month natural conception chances exceeding 30%, immediate treatment with intrauterine insemination (IUI) and controlled ovarian hyperstimulation is not better than expectant management for 6 months. Below the threshold of 30%, treatment with IUI is superior over expectant management, but immediate in vitro fertilization was not better than IUI., Conclusion: In couples with unexplained infertility and a good prognosis for natural conception, treatment can be delayed, whereas in couples with a poor prognosis, immediate treatment (with IUI-controlled ovarian hyperstimulation) is warranted., Relevance: These data indicate that in couples with unexplained infertility, integration of prediction models into clinical decision making can optimize treatment selection and maximize fertility outcomes while limiting unnecessary treatment., Competing Interests: Declaration of Interests N.A. has nothing to disclose. Q.F. declares receiving a Ph.D. scholarship from Merck. L.S. has nothing to disclose. A.M. has nothing to disclose. B.W.M. is supported by a NHMRC Investigator grant (GNT1176437) ; reports consultancy, travel support, and research funding from Merck and Guerbet and consultancy for Organon and Norgine; and holds stocks from ObsEva., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Photoperiod is a crucial environmental cue for phenological responses, including growth cessation and winter dormancy in perennial woody plants. Two regulatory modules within the photoperiod pathway explain bud dormancy induction in poplar (Populus spp.): the circadian oscillator LATE ELONGATED HYPOCOTYL 2 (LHY2) and GIGANTEA-like genes (GIs) both regulate the key target for winter dormancy induction FLOWERING LOCUS T2 (FT2). However, modification of LHY2 and GIs cannot completely prevent growth cessation and bud set under short-day (SD) conditions, indicating that additional regulatory modules are likely involved. We identified PtoHY5a, an orthologs of the photomorphogenesis regulatory factor ELONGATED HYPOCOTYL 5 (HY5) in poplar (Populus tomentosa), that directly activates PtoFT2 expression and represses the circadian oscillation of LHY2, indirectly activating PtoFT2 expression. Thus, PtoHY5a suppresses SD-induced growth cessation and bud set. Accordingly, PtoHY5a knockout facilitates dormancy induction. PtoHY5a also inhibits bud-break in poplar by controlling gibberellic acid (GA) levels in apical buds. Additionally, PtoHY5a regulates the photoperiodic control of seasonal growth downstream of phytochrome PHYB2. Thus, PtoHY5a modulates seasonal growth in poplar by regulating the PtoPHYB2-PtoHY5a-PtoFT2 module to determine the onset of winter dormancy, and by fine-tuning GA levels to control bud-break., Competing Interests: Conflict of interest statement. 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bone nonunion poses an urgent clinical challenge that needs to be addressed. Recent studies have revealed that the metabolic microenvironment plays a vital role in fracture healing. Macrophages and bone marrow-derived mesenchymal stromal cells (BMSCs) are important targets for therapeutic interventions in bone fractures. Itaconate is a TCA cycle metabolite that has emerged as a potent macrophage immunomodulator that limits the inflammatory response. During osteogenic differentiation, BMSCs tend to undergo aerobic glycolysis and metabolize glucose to lactate. Copper ion (Cu 2+ ) is an essential trace element that participates in glucose metabolism and may stimulate glycolysis in BMSCs and promote osteogenesis. In this study, we develop a 4-octyl itaconate (4-OI)@Cu@Gel nanocomposite hydrogel that can effectively deliver and release 4-OI and Cu 2+ to modulate the metabolic microenvironment and improve the functions of cells involved in the fracture healing process. The findings reveal that burst release of 4-OI reduces the inflammatory response, promotes M2 macrophage polarization, and alleviates oxidative stress, while sustained release of Cu 2+ stimulates BMSC glycolysis and osteogenic differentiation and enhances endothelial cell angiogenesis. Consequently, the 4-OI@Cu@Gel system achieves rapid fracture healing in mice. Thus, this study proposes a promising regenerative strategy to expedite bone fracture healing through metabolic reprogramming of macrophages and BMSCs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (© 2024 The Authors.)

Ovarian cancer (OC) is the leading cause of gynecological cancer death. Cancer-associated fibroblasts (CAF) is involved in wound healing and inflammatory processes, tumor occurrence and progression, and chemotherapy resistance in OC. GSE184880 dataset was used to identify CAF-related genes in OC. CAF-related signature (CRS) was constructed using integrative 10 machine learning methods with the datasets from the Cancer Genome Atlas, GSE14764, GSE26193, GSE26712, GSE63885, and GSE140082. The performance of CRS in predicting immunotherapy benefits was verified using 3 immunotherapy datasets (GSE91061, GSE78220, and IMvigor210) and several immune calculating scores. The Lasso + StepCox[forward] method-based predicting model having a highest average C index of 0.69 was referred as the optimal CRS and it had a stable and powerful performance in predicting clinical outcome of OC patients, with the 1-, 3-, and 5-year area under curves were 0.699, 0.708, and 0.767 in the Cancer Genome Atlas cohort. The C index of CRS was higher than that of tumor grade, clinical stage, and many developed signatures. Low CRS score demonstrated lower tumor immune dysfunction and exclusion score, lower immune escape score, higher PD1&CTLA4 immunophenoscore, higher tumor mutation burden score, higher response rate and better prognosis in OC, suggesting a better immunotherapy response. OC patients with low CRS score had a lower half maximal inhibitory concentration value of some drugs (Gemcitabine, Tamoxifen, and Nilotinib, etc) and lower score of some cancer-related hallmarks (Notch signaling, hypoxia, and glycolysis, etc). The current study developed an optimal CRS in OC, which acted as an indicator for the prognosis, stratifying risk and guiding treatment for OC patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Stomach adenocarcinoma (STAD) is one of the subtype of gastric cancer with high invasiveness, extreme heterogeneity, high morbidity, and high mortality. The degradome is the most abundant class of cellular enzymes that play an essential role in regulating cellular activity and carcinogenesis. An integrative machine learning procedure including 10 methods was performed to develop a prognostic degradome-based prognostic signature (DPS) in TCGA, GSE15459, GSE26253, and GSE62254 datasets. Investigations of the DPS concerning immune infiltration, immunotherapy benefits, and drug priority were orchestrated. The DPS developed by Enet [alpha = 0.3] method was regarded as the optimal prognostic model. The DPS had a stable and powerful performance in predicting the clinical outcome of STAD and served as an independent risk factor in training and testing cohorts. The C-index of DPS was higher than that of age, sex, and clinical stage. STAD patients with low DPS scores had a higher abundance of B cells, CD8+ T cells, higher cytolytic scores, and T cell co-stimulation scores. Moreover, low DPS score indicated a lower tumor immune dysfunction and exclusion score, lower T cell dysfunction and exclusion score, higher PD1&CTLA4 immunophenoscore, and higher tumor mutation burden score in STAD, demonstrating a better immunotherapy response. STAD patients with a high DPS score had a lower IC50 value of common chemotherapy and targeted therapy regimens (Cisplatin, Docetaxel, Gefitinib, etc). Our study developed an optimal DPS for STAD. The DPS could predict the prognosis, risk stratification and guide treatment for STAD patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

As an ideal drug carrier, it should possess high drug loading and encapsulation efficiency and precise drug targeting release. Herein, we utilized a template-guided self-weaving technology of phase-separated silk fibroin (SF) in reverse microemulsion (RME) to fabricate a kind of hyaluronic acid (HA) coated SF nanocage (HA-gNCs) for drug delivery of cancer immunotherapy. Due to the hollow structure, HA-gNCs were capable of simultaneous encapsulation of the anti-inflammatory drug betamethasone phosphate (BetP) and the immune checkpoint blockade (ICB) agent PD-L1 antibody (αPD-L1) efficiently. Another point worth noting was that the thiocarbonate cross-linkers used to strengthen the SF shell of HA-gNCs could be quickly broken by overexpressed glutathione (GSH) to reach responsive drug release inside tumor tissues accompanied by hydrogen sulfide (H 2 S) production in one step. The synergistic effect of released BetP and generated H 2 S guaranteed chronological modulation of the immunosuppressive tumor microenvironment (ITME) to amplify the therapeutic effect of αPD-L1 for the growth, metastasis, and recurrence of tumors. This study highlighted the exceptional prospect of HA-gNCs as a self-assistance platform for cancer drug delivery.

Bone homeostasis is maintained by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. A dramatic decrease in estrogen levels in postmenopausal women leads to osteoclast overactivation, impaired bone homeostasis, and subsequent bone loss. Changes in the gut microbiome affect bone mineral density. However, the role of the gut microbiome in estrogen deficiency-induced bone loss and its underlying mechanism remain unknown. In this study, we found that the abundance of Clostridium sporogenes (C. spor.) and its derived metabolite, indole propionic acid (IPA), were decreased in ovariectomized (OVX) mice. In vitro assays suggested that IPA suppressed osteoclast differentiation and function. At the molecular level, IPA suppressed receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced pregnane X receptor (PXR) ubiquitination and degradation, leading to increased binding of remaining PXR with P65. In vivo daily IPA administration or repeated C. spor. colonization protected against OVX-induced bone loss. To protect live bacteria from the harsh gastric environment and delay the emptying of orally administered C. spor. from the intestine, a C. spor.-encapsulated silk fibroin (SF) hydrogel system was developed, which achieved bone protection in OVX mice comparable to that achieved with repeated germ transplantation or daily IPA administration. Overall, we found that gut C. spor.-derived IPA was involved in estrogen deficiency-induced osteoclast overactivation by regulating the PXR/P65 complex. The C. spor.-encapsulated SF hydrogel system is a promising tool for combating postmenopausal osteoporosis without the disadvantages of repeated germ transplantation., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Avian coccidiosis, caused by Eimeria parasites, continues to devastate the poultry industry and results in significant economic losses. Ionophore coccidiostats, such as maduramycin and monensin, are widely used for prophylaxis of coccidiosis in poultry. Nevertheless, their efficacy has been challenged by widespread drug resistance. However, the underlying mechanisms have not been revealed. Understanding the targets and resistance mechanisms to anticoccidials is critical to combat this major parasitic disease. In the present study, maduramycin-resistant (MRR) and drug-sensitive (DS) sporozoites of Eimeria tenella were purified for transcriptomic and metabolomic analysis. The transcriptome analysis revealed 5016 differentially expressed genes (DEGs) in MRR compared to DS, and KEGG pathway enrichment analysis indicated that DEGs were involved in spliceosome, carbon metabolism, glycolysis, and biosynthesis of amino acids. In the untargeted metabolomics assay, 297 differentially expressed metabolites (DEMs) were identified in MRR compared to DS, and KEGG pathway enrichment analysis indicated that these DEMs were involved in 10 pathways, including fructose and mannose metabolism, cysteine and methionine metabolism, arginine and proline metabolism, and glutathione metabolism. Targeted metabolomic analysis revealed 14 DEMs in MRR compared to DS, and KEGG pathway analysis indicated that these DEMs were involved in 20 pathways, including fructose and mannose metabolism, glycolysis/gluconeogenesis, and carbon metabolism. Compared to DS, energy homeostasis and amino acid metabolism were differentially regulated in MRR. Our results provide gene and metabolite expression landscapes of E. tenella following maduramycin induction. This study is the first work involving integrated transcriptomic and metabolomic analyses to identify the key pathways to understand the molecular and metabolic mechanisms underlying drug resistance to polyether ionophores in coccidia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In adult mammals, injured retinal ganglion cells (RGCs) fail to spontaneously regrow severed axons, resulting in permanent visual deficits. Robust axon growth, however, is observed after intra-ocular injection of particulate β-glucan isolated from yeast. Blood-borne myeloid cells rapidly respond to β-glucan, releasing numerous pro-regenerative factors. Unfortunately, the pro-regenerative effects are undermined by retinal damage inflicted by an overactive immune system. Here, we demonstrate that protection of the inflamed vasculature promotes immune-mediated RGC regeneration. In the absence of microglia, leakiness of the blood-retina barrier increases, pro-inflammatory neutrophils are elevated, and RGC regeneration is reduced. Functional ablation of the complement receptor 3 (CD11b/integrin-αM), but not the complement components C1q -/- or C3 -/- , reduces ocular inflammation, protects the blood-retina barrier, and enhances RGC regeneration. Selective targeting of neutrophils with anti-Ly6G does not increase axogenic neutrophils but protects the blood-retina barrier and enhances RGC regeneration. Together, these findings reveal that protection of the inflamed vasculature promotes neuronal regeneration., Competing Interests: Declaration of interests Particulate and soluble β-(1,3)(1,6)-glucans were provided by ImmunoResearch, Inc., MN 55121, USA, under a collaborative research agreement. The PLX5622 compound was provided by Plexxikon, Inc., San Francisco, California, USA. Neither ImmunoResearch, Inc., nor Plexxikon, Inc., had any input in experimental design, data acquisition, interpretation, or presentation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In situ monitoring of bone regeneration enables timely diagnosis and intervention by acquiring vital biological parameters. However, an existing gap exists in the availability of effective methodologies for continuous and dynamic monitoring of the bone tissue regeneration process, encompassing the concurrent visualization of bone formation and implant degradation. Here, we present an integrated scaffold designed to facilitate real-time monitoring of both bone formation and implant degradation during the repair of bone defects. Laponite (Lap), CyP-loaded mesoporous silica (CyP@MSNs) and ultrasmall superparamagnetic iron oxide nanoparticles (USPIO@SiO 2 ) were incorporated into a bioink containing bone marrow mesenchymal stem cells (BMSCs) to fabricate functional scaffolds denoted as C@M/GLU using 3D bioprinting technology. In both in vivo and in vitro experiments, the composite scaffold has demonstrated a significant enhancement of bone regeneration through the controlled release of silicon (Si) and magnesium (Mg) ions. Employing near-infrared fluorescence (NIR-FL) imaging, the composite scaffold facilitates the monitoring of alkaline phosphate (ALP) expression, providing an accurate reflection of the scaffold's initial osteogenic activity. Meanwhile, the degradation of scaffolds was monitored by tracking the changes in the magnetic resonance (MR) signals at various time points. These findings indicate that the designed scaffold holds potential as an in situ bone implant for combined visualization of osteogenesis and implant degradation throughout the bone repair process., 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., (© 2024 The Authors.)

Background: Ultrasound three-dimensional visualization, a cutting-edge technology in medical imaging, enhances diagnostic accuracy by providing a more comprehensive and readable portrayal of anatomical structures compared to traditional two-dimensional ultrasound. Crucial to this visualization is the segmentation of multiple targets. However, challenges like noise interference, inaccurate boundaries, and difficulties in segmenting small structures exist in the multi-target segmentation of ultrasound images. This study, using neck ultrasound images, concentrates on researching multi-target segmentation methods for the thyroid and surrounding tissues., Method: We improved the Unet++ to propose PA-Unet++ to enhance the multi-target segmentation accuracy of the thyroid and its surrounding tissues by addressing ultrasound noise interference. This involves integrating multi-scale feature information using a pyramid pooling module to facilitate segmentation of structures of various sizes. Additionally, an attention gate mechanism is applied to each decoding layer to progressively highlight target tissues and suppress the impact of background pixels., Results: Video data obtained from 2D ultrasound thyroid serial scans served as the dataset for this paper.4600 images containing 23,000 annotated regions were divided into training and test sets at a ratio of 9:1, the results showed that: compared with the results of U-net++, the Dice of our model increased from 78.78% to 81.88% (+ 3.10%), the mIOU increased from 73.44% to 80.35% (+ 6.91%), and the PA index increased from 92.95% to 94.79% (+ 1.84%)., Conclusions: Accurate segmentation is fundamental for various clinical applications, including disease diagnosis, treatment planning, and monitoring. This study will have a positive impact on the improvement of 3D visualization capabilities and clinical decision-making and research in the context of ultrasound image., (© 2024. The Author(s).)

The rheumatoid arthritis (RA) microenvironment is often followed by a vicious circle of high inflammation, endogenous gas levels imbalance, and poor treatment. To break the circle, we develop a dual-gas-mediated injectable hydrogel for modulating the immune microenvironment of RA and simultaneously releasing therapeutic drugs. The hydrogel (DNRS gel) could be broken down on-demand by consuming excessive nitric oxide (NO) and releasing therapeutic hydrogen sulfide (H 2 S), resulting in endogenous gas restoration, inflammation alleviation, and macrophage polarization to M2 type. Additionally, the hydrogel could suppress osteoclastogenesis and enhance osteogenesis. Furthermore, the intra-articularly injected hydrogel with methotrexate (MTX/DNRS gel) significantly alleviated inflammation and clinical symptoms and promoted the repair of bone erosion in the collagen-induced arthritis rat model. As a result, in vivo results demonstrated that MTX/DNRS gel restored the microenvironment and improved the therapeutic effect of MTX. This study provides a novel understanding of developing versatile smart delivery platforms for RA treatment., 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., (© 2024 The Authors.)

Stomach adenocarcinoma (STAD) is a one of most common malignancies with high mortality-to-incidence ratio. Programmed cell death (PCD) exerts vital functions in the progression of cancer. The role of PCD-related genes (PRGs) in STAD are not fully clarified. Using TCGA, GSE15459, GSE26253, GSE62254 and GSE84437 datasets, PCD-related signature (PRS) was constructed with an integrative procedure including 10 machine learning methods. The role of PRS in predicting the immunotherapy benefits was evaluated by several predicting score and 3 immunotherapy datasets (GSE91061, GSE78220, and IMvigor210). The model developed by Lasso + CoxBoost algorithm having a highest average C-index of 0.66 was considered as the optimal PRS. As an independent risk factor for STAD patients, PRS had a good performance in predicting the overall survival rate of patients, with an AUC of 1-, 3-, and 5-year ROC curve being 0.771, 0.751 and 0.827 in TCGA cohort. High PRS score demonstrated a lower gene set score of some immune-activated cells and immune-activated activities. Patient with high PRS score had a higher TIDE score, higher immune escape score, lower PD1&CTLA4 immunophenoscore, lower TMB score, lower response rate and poor prognosis, indicating a less immunotherapy response. The IC50 value of some drugs correlated with chemotherapy and targeted therapy was higher in high PRS score group. Our investigation developed an optimal PRS in STAD and it acted as an indicator for predicting the prognosis, stratifying risk and guiding treatment for STAD patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Proper compartmentalization of the sperm flagellum is essential for fertility. The annulus is a septin-based ring that demarcates the midpiece (MP) and the principal piece (PP). It is assembled at the flagellar base, migrates caudally, and halts upon arriving at the PP. However, the mechanisms governing annulus positioning remain unknown. We report that a Chibby3 (Cby3)/Cby1-interacting BAR domain-containing 1 (ciBAR1) complex is required for this process. Ablation of either gene in mice results in male fertility defects, caused by kinked sperm flagella with the annulus mispositioned in the PP. Cby3 and ciBAR1 interact and colocalize to the annulus near the curved membrane invagination at the flagellar pocket. In the absence of Cby3, periannular membranes appear to be deformed, allowing the annulus to migrate over the fibrous sheath into the PP. Collectively, our results suggest that the Cby3/ciBAR1 complex regulates local membrane properties to position the annulus at the MP/PP junction., (© 2024 Hoque et al.)

In situ monitoring of bone tissue regeneration progression is critical for the development of bone tissue engineering scaffold. However, engineered scaffolds that can stimulate osteogenic progress and allow for non-invasive monitoring of in vivo bone regeneration simultaneously are rarely reported. Based on a hard-and-soft integration strategy, a multifunctional scaffold composed of 3D printed microfilaments and a hydrogel network containing simvastatin (SV), indocyanine green-loaded superamphiphiles, and aminated ultrasmall superparamagnetic iron oxide nanoparticles (USPIO-NH 2 ) is fabricated. Both in vitro and in vivo results demonstrate that the as-prepared scaffold significantly promotes osteogenesis through controlled SV release. The biocomposite scaffold exhibits alkaline phosphatase-responsive near-infrared II fluorescence imaging. Meanwhile, USPIO-NH 2 within the co-crosslinked nanocomposite network enables the visualization of scaffold degradation by magnetic resonance imaging. Therefore, the biocomposite scaffold enables or facilitates non-invasive in situ monitoring of neo-bone formation and scaffold degradation processes following osteogenic stimulation, offering a promising strategy to develop theranostic scaffolds for tissue engineering., (© 2023 Wiley-VCH GmbH.)

IVF is the backbone of infertility treatment, but due to its costs, it is not affordable for everyone. The cost of IVF is further escalated by interventions added to the routine treatment, which are claimed to boost pregnancy rates, so-called add-ons. Consequently, it is critical to offset the increased costs of an intervention against a potentially higher benefit. Here, we propose using a simplified framework considering the cost of a standard IVF procedure to create one live-born baby as a benchmark for the cost-effectiveness of other fertility treatments, add-ons inclusive. This framework is a simplified approach to a formal economic evaluation, enabling a rapid assessment of cost effectiveness in clinical settings. For a 30-year-old woman, assuming a 44.6% cumulative live birth rate and a cost of $12 000 per complete cycle, the cost to create one live-born baby would be ∼$27 000 (i.e. willingness to pay). Under this concept, the decision whether to accept or reject a new treatment depends from an economic perspective on the incremental cost per additional live birth from the new treatment/add-on, with the $27 000 per live-born baby as a reference threshold. This threshold can vary with women's age, and other factors such as the economic perspective and risk of side effects can play a role. If a new add-on or treatment costs >$27 000 per live birth, it might be more rational to invest in a new IVF cycle rather than spending on the add-on. With the increasing number of novel technologies in IVF and the lack of a rapid approach to evaluate their cost-effectiveness, this simplified framework will help with a more objective assessment of the cost-effectiveness of infertility treatments, including add-ons., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

To fill the knowledge gaps regarding the global patterns of human exposure to flame retardants (FRs) (i.e., brominated flame retardants (BFRs) and organophosphorus flame retardants (OPFRs)), data on the levels and distributions of FRs in external and internal exposure mediums, including indoor dust, indoor air, skin wipe, serum and urine, were summarized and analysed. Comparatively, FR levels were relatively higher in developed regions in all mediums, and significant positive correlations between FR contamination and economic development level were observed in indoor dust and air. Over time, the concentration of BFRs showed a slightly decreasing trend in all mediums worldwide, whereas OPFRs represented an upward tendency in some regions (e.g., the USA and China). The occurrence levels of FRs and their metabolites in all external and internal media were generally correlated, implying a mutual indicative role among them. Dermal absorption generally contributed >60% of the total exposure of most FR monomers, and dust ingestion was dominant for several low volatile compounds, while inhalation was found to be negligible. The high-risk FR monomers (BDE-47, BDE-99 and TCIPP) identified by external exposure assessment showed similarity to the major FRs or metabolites observed in internal exposure mediums, suggesting the feasibility of using these methods to characterize human exposure and the contribution of indoor exposure to the human burden of FRs. This review highlights the significant importance of exposure assessment based on multiple mediums for future studies., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

As for the deep tissue infections of chronic osteomyelitis, antibiotics are hard to deliver into the infected bone tissue, which makes it difficult to be cured completely in clinic. Microwave has strong penetration, and the medium can produce a good bactericidal effect through the microwave thermal effect (MTE). Here, a new microwave sensitizer (Fe 3 O 4 @APNs) was prepared and evaluated. Black phosphorus nanosheets modified with phytic acid dodecasodium (APNs) were fabricated by a liquid-phase exfoliation method that exhibited good water oxygen stability. A complex with Fe 3 O 4 compound and APNs (Fe 3 O 4 @APNs) was formed by an ultrasonic mixing process, which showed excellent MTE (quickly increased to 53.5 °C in 5 min at 2.45 GHz, 10 W/cm 2 ) via dielectric versus magnetic loss (reflect loss value of -5.94 dB at 2.45 GHz). The Fe 3 O 4 @APNs microwave sensitizer developed in this study has an outstanding in vitro antibacterial effect and might show promise for the treatment of chronic osteomyelitis enabled by local tissue heating via the MTE.

Objective: To explore the genetic basis for a fetus featuring oligodactyly., Methods: A fetus with hand deformity identified by ultrasound at the Maternal and Child Health Care Hospital of Hubei Province on October 20, 2018 was selected as the study subject. Clinical information and ultrasonographic finding of the pregnant woman were collected. Following elected abortion, umbilical cord and peripheral venous blood samples of the couple were collected for the extraction of genomic DNA. Copy number variation sequencing (CNV-seq) and trio-whole exome sequencing (trio-WES) were carried out. Candidate variants were verified by Sanger sequencing., Results: Ultrasonographic examination at 30 +2 weeks of gestation revealed that the fetus had small right hand with absence of 2nd-5th fingers, whilst its left hand had appeared to be normal. By CNV-seq, no pathogenic or likely pathogenic copy number variation (CNV) (≥ 100 Kb) was detected in the fetus. Trio-WES revealed that the fetus had harbored a novel heterozygous c.3298G>A (p.Val1100Met) variant of the SMC3 gene. The variant has not been recorded in the population databases, and was predicted to be deleterious by several bioinformatic software and evolutionarily conserved based on multiple sequence alignment analysis. Sanger sequencing showed that neither parent has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS2+PM2&#95;Supporting+PP3)., Conclusion: The fetus was diagnosed with Cornelia de Lange syndrome, for which the novel heterozygous c.3298G>A variant of the SMC3 gene may be accountable.

Tissue engineering holds great potential for tissue repair and rejuvenation. Plant-derived exosome-like nanoparticles (ELNs) have recently emerged as a promising avenue in tissue engineering. However, there is an urgent need to understand how plant ELNs can be therapeutically applied in clinical disease management, especially for tissue regeneration. In this review, we comprehensively examine the properties, characteristics, and isolation techniques of plant ELNs. We also discuss their impact on the immune system, compatibility with the human body, and their role in tissue regeneration. To ensure the suitability of plant ELNs for tissue engineering, we explore various engineering and modification strategies. Additionally, we provide insights into the progress of commercialization and industrial perspectives on plant ELNs. This review aims to highlight the potential of plant ELNs in regenerative medicine by exploring the current research landscape and key findings., Competing Interests: The authors declare that there are no conflicts of interest for this work., (© 2024 Feng et al.)

Background: Cognitive impairment arising from cerebral small vessel disease (CSVD) represents a critical subtype of vascular cognitive impairments (VCI) and is the primary cause of vascular dementia. However, identifying reliable clinical and laboratory indicators for this disease remain elusive. We hypothesize that plasma exosome proteins hold the potential to serve as biomarkers for the onset of cognitive dysfunction associated with cerebrovascular diseases., Methods: We employed TMT-based proteomics to discern variations in serum exosome proteomes between individuals with cognitive impairments due to CSVD and healthy volunteers., Results: Each group comprised 18 subjects, and through differential expression analysis, we identified 22 down-regulated and 8 up-regulated proteins between the two groups. Our research revealed 30 differentially expressed plasma exosome proteins, including histone, proteasome, clusterin and coagulation factor XIII, in individuals with cognitive impairments caused by CSVD., Conclusion: The 30 differentially expressed plasma exosome proteins identified in our study are promising as biomarkers for diagnosing cognitive impairments resulting from CSVD. These findings may help us better understand the underlying pathological mechanisms involved in the diseases., 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.)

Ischemic stroke is a devastative nervous system disease associated with high mortality and morbidity rates. Unfortunately, no clinically effective neuroprotective drugs are available now. In ischemic stroke, S100 calcium-binding protein b (S100b) binds to receptor for advanced glycation end products (Rage), leading to the neurological injury. Therefore, disruption of the interaction between S100B and Rage can rescue neuronal cells. Here, we designed a peptide, termed TAT-W61, derived from the V domain of Rage which can recognize S100b. Intriguingly, TAT-W61 can reduce the inflammatory caused by ischemic stroke through the direct binding to S100b. The further investigation demonstrated that TAT-W61 can improve pathological infarct volume and reduce the apoptotic rate. Particularly, TAT-W61 significantly improved the learning ability, memory, and motor dysfunction of the mouse in the ischemic stroke model. Our study provides a mechanistic insight into the abnormal expression of S100b and Rage in ischemic stroke and yields an invaluable candidate for the development of drugs in tackling ischemic stroke. KEY MESSAGES: S100b expression is higher in ischemic stroke, in association with a high expression of many genes, especially of Rage. S100b is directly bound to the V-domain of Rage. Blocking the binding of S100b to Rage improves the injury after ischemic stroke., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The clinical treatment of bone defects presents ongoing challenges. One promising approach is bone tissue engineering (BTE), wherein hydrogels have garnered significant attention. However, the application of hydrogels in BTE is severely limited due to their poor mechanical properties, as well as their inferior proangiogenic and osteogenic activities. To address these limitations, our develop a dual cross-linked alendronate (ALN)-Ca 2+ /Mg 2+ -doped sulfated hyaluronic acid (SHA@CM) hydrogel, using a one-step mixing injection molding method known as "three-in-one" approach. This approach enabled the simultaneous formation of Schiff-Base crosslinking and electric attraction-based crosslinking within the hydrogel. The Schiff-Base crosslinking contributed to the majority of the hydrogel's mechanical strength, while the electric attraction-based crosslinking served as a release reservoir for Ca 2+ /Mg 2+ and ALN, promoting enhanced osteogenic activities and providing additional mechanical reinforcement to the hydrogel. These experimental data demonstrates several favorable properties of the SHA@CM hydrogel, including satisfactory injectability, rapid gelation, self-healing capacity, and excellent cytocompatibility. Moreover, the presence of sulfated groups and Mg 2+ within the SHA@CM hydrogel exhibited pro-angiogenic effects, while the controlled release of nanoparticles formed by Ca 2+ /Mg 2+ and ALN further enhanced the osteogenesis of the hydrogel. Overall, these results indicate that the SHA@CM hydrogel holds significant potential for the clinical translation of BTE., (© 2023 Wiley-VCH GmbH.)

Evodia lepta Merr. (Evodia lepta) is a well-known traditional Chinese medicine, which has been widely used in herbal tea. We previously reported that the coumarin compounds from the root of Evodia lepta exhibited neuroprotective effects. However, whether Evodia lepta could inhibit NLRP3 inflammasome in dementia was still unknown. In this study, the components of the Evodia lepta extract were identified by HPLC-Q-TOF HRMS. We employed a scopolamine-treated mouse model. Evodia lepta extract (10 or 20 mg/kg) and donepezil were treated by gavage once a day for 14 consecutive days. Following the behavioral tests, oxidative stress levels were measured. Then, Western blot and immunofluorescence analysis were used to evaluate the expressions of NLRP3 inflammasome. 14 major components of the Evodia lepta extract were identified by HPLC-Q-TOF HRMS. The results of Morris water maze, object recognition task and open field test indicated that Evodia lepta extract could ameliorate cognitive impairment in scopolamine-treated mice. Evodia lepta extract improved cholinergic system. Moreover, Evodia lepta extract improved the expressions of PSD95 and BDNF. Evodia lepta extract suppressed neuronal oxidative stress and apoptosis. In addition, Evodia lepta extract inhibited NLRP3 inflammasome in the hippocampus of scopolamine-treated mice. Evodia lepta extract could protect against cognitive impairment by inhibiting NLRP3 inflammasome in scopolamine-treated mice.