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Cerebrovascular image segmentation is one of the crucial tasks in the field of biomedical image processing. Due to the variable morphology of cerebral blood vessels, the traditional convolutional kernel is weak in perceiving the structure of elongated blood vessels in the brain, and it is easy to lose the feature information of the elongated blood vessels during the network training process. In this paper, a vascular convolutional U-network (VCU-Net) is proposed to address these problems. This network utilizes a new convolution (vascular convolution) instead of the traditional convolution kernel, to extract features of elongated blood vessels in the brain with different morphologies and orientations by adaptive convolution. In the network encoding stage, a new feature splicing method is used to combine the feature tensor obtained through vascular convolution with the original tensor to provide richer feature information. Experiments show that the DSC and IOU of the proposed method are 53.57% and 69.74%, which are improved by 2.11% and 2.01% over the best performance of the GVC-Net among several typical models. In image visualization, the proposed network has better segmentation performance for complex cerebrovascular structures, especially in dealing with elongated blood vessels in the brain, which shows better integrity and continuity., (© 2024. International Federation for Medical and Biological Engineering.)

Sjögren's syndrome (SS) is a chronic autoimmune disease caused by immune system disorders. The main clinical manifestations of SS are dry mouth and eyes caused by the destruction of exocrine glands, such as the salivary and lacrimal glands, and systemic manifestations, such as interstitial pneumonia, interstitial nephritis and vasculitis. The pathogenesis of this condition is complex. However, this has not been fully elucidated. Treatment mainly consists of glucocorticoids, disease-modifying antirheumatic drugs and biological agents, which can only control inflammation but not repair the tissue. Therefore, identifying methods to regulate immune disorders and repair damaged tissues is imperative. Cell therapy involves the transplantation of autologous or allogeneic normal or bioengineered cells into the body of a patient to replace damaged cells or achieve a stronger immunomodulatory capacity to cure diseases, mainly including stem cell therapy and immune cell therapy. Cell therapy can reduce inflammation, relieve symptoms and promote tissue repair and regeneration of exocrine glands such as the salivary glands. It has broad application prospects and may become a new treatment strategy for patients with SS. However, there are various challenges in cell preparation, culture, storage and transportation. This article reviews the research status and prospects of cell therapies for SS.

Pregnancy is extremely vulnerable to external environmental influences. Bisphenol A, an endocrine-disrupting chemical, poses a significant environmental hazard to individuals of all ages and stages, particularly during pregnancy. The placenta is a temporary organ facilitating the connection between the mother and fetus. While it can detoxify certain exogenous substances, it is also vulnerable to the impacts of endocrine disruptors. Likewise, the intestinal flora is highly sensitive to exogenous stresses and environmental pollutants. The regulation of gut microbiota plays a crucial role in ensuring the health of both the mother and the fetus. The gut-placental axis connects the gut, gut microbes, placenta, and fetus. Exploring possible effects on placental function and fetal development involves analyzing changes in gut microbiota composition. Given that bisphenol A may cross the intestine and affect intestinal function, gut microorganisms, and their metabolites, as well as its potential impact on the placenta, resulting in impaired placental function and fetal development, this study aims to establish a link between bisphenol A exposure, intestinal microorganisms, placental function, and fetal development. This paper seeks to analyze the effects of maternal exposure to bisphenol A during pregnancy on the balance of the maternal gut microbiota, placental function, and fetal development, considering the key role of the gut-placental axis. Additionally, this paper proposes potential directions for future research emphasizing the importance of mitigating the adverse outcomes of bisphenol A exposure during pregnancy in both human and animal 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 © 2024 Elsevier Inc. All rights reserved.)

Heavy metal ions are one of the main sources of water pollution, which has become a major global problem. Given the growing need for heavy metal ion detection, electrochemical sensor stands out for its high sensitivity and efficiency. Metal-organic frameworks (MOFs) have garnered much interest as electrode modifiers for electrochemical detection of heavy metal ions owing to their significant specific surface area, tailored pore size, and catalytic activity. This review summarizes the progress of MOF-based materials, including pristine MOFs and MOF composites, in the electrochemical detection of various heavy metal ions. The synthetic methods of pristine MOFs, the detection mechanisms of heavy metal ions and the modification strategies of MOFs are introduced. Besides, the diverse applications of MOF-based materials in detecting both single and multiple heavy metal ions are presented. Furthermore, we present the current challenges and prospects for MOF-based materials in electrochemical heavy metal ion detection., 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.)

Recently, Ru single atoms supported on carbon nanomaterials have demonstrated ultrahigh activity for acid hydrogen evolution reaction (HER), however their neutral HER activity remains low due to the sluggish kinetics for both the water dissociation step to generate H* intermediates and subsequent H* recombination in neutral electrolytes. Here, we synthesize ordered low-coordinated Ru atom arrays confined in Mn oxides (i.e., Li4Mn5O12) for concurrently boosting the water dissociation and H* recombination, thus achieving a 6-fold HER activity enhancement than commercial Pt/C in neutral media. Control experiments indicate that low-coordinated Ru atoms with strong affinity to oxygen atoms of water molecules facilitate the water dissociation to rapidly generate H*. More importantly, both electrochemical and theoretic results uncover that the array-like structure allows the activation of two water molecules on two adjacent Ru atoms for enabling direct H*-H* recombination via the Tafel step, while isolated Ru atoms can only activate water one by one for recombining H* via the sluggish Heyrovsky step. Clearly, this work paves new avenues to boosting the electrocatalytic activity by constructing ordered metal atoms assembles with controllable coordination environments., (© 2024 Wiley‐VCH GmbH.)

Due to the scarcity of yak milk in Tibetan areas, local herders primarily use traditional freezing methods for preservation. However, the extent of microbial contamination in raw yak milk during frozen storage and its impact on milk quality remains largely unexplored. This study analyzed the changes in bacterial populations and quality of raw yak milk stored at -18 °C for 6 months. The results indicated that, compared to fresh milk, the freshness of yak milk showed no significant change after 2 months of frozen storage (P > 0.05). After 4 months, the bacterial diversity of flora in yak milk increased significantly, with Pseudomonas and Acinetobacter emerging as the dominant psychrophilic bacteria. Correspondingly, the expression of metabolic pathways related to quality deterioration increased, with a significant increase in physicochemical indicators such as acidity, proteolysis degree, acid value and fat oxidation degree (P < 0.05). Extending the frozen storage to 6 months resulted in a slight but no significant decrease in bacterial diversity, with no significant difference in quality deterioration compared to the 4-month group (P > 0.05). Correlation analysis further revealed that Acinetobacter and Psychrobacter were significantly positively correlated with quality deterioration of frozen milk (P < 0.05). In summary, when frozen for more than 4 months, raw yak milk exhibited the highest bacterial diversity and predicted the most abundant metabolic pathways, with dominant psychrophilic bacteria massive proliferation leading to a decline in quality and safety., 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.)

Carbon dots (CDs) has been widely utilized in multiple fields, especially towards kinds of drug analyses, owing to its superior optical properties and satisfactory stability. Herein, we rapidly synthesized one kind of soluble bright-blue fluorescent CDs through a facile microwave method, while disodium ethylenediaminetetraacetic acid and phosphoric acid served as the raw materials. Importantly, introducing ranitidine into these CDs resulted in its decreased fluorescence, and thus an innovative method of detecting ranitidine was successfully established, which showed the favorable selectivity and anti-interference ability. With the optimal conditions, the standard curve diagram of F 0 /F against concentration of ranitidine was linear in the range of 6-2000 µM with a correlation coefficient of 0.9833, and the limit of detection (LOD) was calculated to be 4.2 µM. Meanwhile, we also explored the detecting mechanism of ranitidine by CDs, and elaborated that as the internal filtration effect. Consequently, we may broaden the avenues of detecting ranitidine on the basis of CDs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sulfur-based aqueous batteries (SABs) are promising for safe, low-cost, and high-capacity energy storage. However, the low output voltage of sulfur cannot meet the demands of high-energy cathode applications due to its intrinsic negative potential (E 0 = -0.51 V vs SHE) of low-valent polysulfide redox (S 2- /S 0 ). Here, instead of relying on traditional aqueous polysulfide redox, for the first time, we demonstrate a high-valent thiosulfate redox (S 2 O 3 2- /S 4 O 6 2- ) electrochemistry, exhibiting positive redox potential (E 0 > 0 V vs SHE) and reversible cation storage in aqueous environment. Operando X-ray absorption fine structure spectroscopy, in situ Raman spectroscopy, and density functional theory calculations reveal the high reversibility and dynamic charge transfer process of high-valent thiosulfate redox. Significantly, the aqueous thiosulfate redox exhibits a high operating voltage of approximately 1.4 V, a reversible capacity of 193 Ah L -1 , and a long cycling life of over 1000 cycles (99.6% capacity retention). This work provides new insights into the high-valent S-based electrochemistry and opens a new pathway to achieve energetic aqueous batteries.

Morphological control of metal-organic frameworks (MOFs) at the micro/nanoscopic scale is critical for optimizing the electrochemical properties of them and their derivatives. In this study, manganese organic phosphate (Mn-MOP) with three distinct two-dimensional (2D) morphologies was synthesized by varying the molar ratio of Mn 2+ to phenyl phosphonic acid, and one of the morphologies is a unique palm leaf shape. In addition, a series of 2D Mn-MOP derivatives were obtained by calcination in air at different temperatures. Electrochemical studies showed that 2D Mn-MOP derivative calcined at 550 °C and exhibited a superior specific capacitance of 230.9 F g -1 at 0.5 A g -1 in 3 M KOH electrolyte. The aqueous asymmetric supercapacitor and the constructed flexible solid-state device demonstrated excellent rate performance. This performance reveals the promising application of 2D Mn-MOP materials for energy storage.

Membranes with precise Li + /Na + and Li + /K + separations are imperative for lithium extraction from brine to address the lithium supply shortage. However, achieving this goal remains a daunting challenge due to the similar valence, chemical properties, and subtle atomic-scale distinctions among these monovalent cations. Herein, inspired by the strict size-sieving effect of biological ion channels, a membrane is presented based on nonporous crystalline materials featuring structurally rigid, dimensionally confined, and long-range ordered ion channels that exclusively permeate naked Li + but block Na + and K + . This naked-Li + -sieving behavior not only enables unprecedented Li + /Na + and Li + /K + selectivities up to 2707.4 and 5109.8, respectively, even surpassing the state-of-the-art membranes by at least two orders of magnitude, but also demonstrates impressive Li + /Mg 2+ and Li + /Ca 2+ separation capabilities. Moreover, this bioinspired membrane has to be utilized for creating a one-step lithium extraction strategy from natural brines rich in Na + , K + , and Mg 2+ without utilizing chemicals or creating solid waste, and it simultaneously produces hydrogen. This research has proposed a new type of ion-sieving membrane and also provides an envisioning of the design paradigm and development of advanced membranes, ion separation, and lithium extraction., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Helicobacter pylori (HP), a common microanaerobic bacteria that lives in the human mouth and stomach, is reported to infect ≈50% of the global population. The current diagnostic methods for HP are either invasive, time-consuming, or harmful. Therefore, a noninvasive and label-free HP diagnostic method needs to be developed urgently. Herein, reduced graphene oxide (rGO) is composited with different metal-based materials to construct a graphene-based electronic nose (e-nose), which exhibits excellent sensitivity and cross-reactive response to several gases in exhaled breath (EB). Principal component analysis (PCA) shows that four typical types of gases in EB can be well discriminated. Additionally, the potential of the e-nose in label-free detection of HP infection is demonstrated through the measurement and analysis of EB samples. Furthermore, a prototype of an e-nose device is designed and constructed for automatic EB detection and HP diagnosis. The accuracy of the prototype machine integrated with the graphene-based e-nose can reach 92% and 91% in the training and validation sets, respectively. These results demonstrate that the highly sensitive graphene-based e-nose has great potential for the label-free diagnosis of HP and may become a novel tool for non-invasive disease screening and diagnosis., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The aim of this study was to investigate the changes of untreated and steamed (100 °C, 20 min), fried (150 °C, 10 min), and baked (200 °C, 30 min) sweet potato polysaccharides during in vitro digestion and their effects on the intestinal flora. The results showed that the reducing sugar content of all four sweet potato polysaccharides increased significantly during digestion. During in vitro fecal fermentation, the content of reducing sugars and total carbohydrates decreased significantly. It indicated that all four polysaccharides showed degradation of polysaccharides during fermentation. Compared to the blank group, the total SCFAs content of the four polysaccharide sample groups was significantly increased. It was worth noting that sweet potato polysaccharides increased the percentage of Bacteroidetes and decreased the percentage of Proteobacteria in the intestinal flora. The findings provide evidence that sweet potato polysaccharides regulate intestinal flora and maintain intestinal health through interactions with intestinal flora., 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.)

Inspired by the iron porphyrin structure of natural horseradish peroxidase (HRP), an efficient carbon-based nanozyme was fabricated using nitrogen-doped graphene quantum dots (NGQDs) and iron ion (Fe 3+ ) nanocomposite, enabling selective distinguishment of hydroquinone (HQ) from its isomers. NGQDs with good dispersibility and uniform size were synthesized via a one-step hydrothermal process. NGQDs lacked peroxidase-like activity but the formed nanocomposite (Fe 3+ -NGQDs) upon Fe 3+ addition possessed high peroxidase-like activity. Fe 3+ -NGQDs nanocomposite exhibited shuttle-shaped structure (∼30 nm), the lattice structure of NGQDs and electron transfer between Fe 3+ and NGQDs. The Fe 3+ -NGQDs nanocomposite can catalyze the production of superoxide radicals (•O 2 - ) from H 2 O 2 . The Michaelis constant (K m ) of Fe 3+ -NGQDs (0.115 mM) was lower than that of natural HRP (0.434 mM) with 3,3',5,5'-tetramethylbenzidine (TMB) as the substrate and the maximum initial reaction rate (V max , 16.47 × 10 -8  M/s) was nearly 4 times higher than that of HRP using H 2 O 2 substrate. HQ, unlike its isomers catechol (CC) and resorcinol (RE), could consume •O 2 - generated from the decomposition of H 2 O 2 catalyzed by Fe 3+ -NGQDs nanocomposite, reducing the oxidation of TMB. This principle enabled selective colorimetric determination of HQ ranged from 1 μM to 70 μM and a limit of detection (LOD) of 0.2 μM. Successful determination of HQ in pond water was also realized., 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.)

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arteriovenous thrombosis and pathological pregnancy, accompanied by persistent antiphospholipid antibodies, (aPL). The incidence of APS is increasing year by year, clinicians lack of understanding of this type of disease, easy to misdiagnose and miss the diagnosis. Therefore, it is extremely important to establish a suitable animal model to reduce the process of disease development as much as possible and improve clinicians' understanding and understanding. This review will summarize the animal models of APS from the aspects of modeling methods, modeling mechanism, evaluation indicators and advantages and disadvantages of methods, providing a reference for finding an animal model highly similar to human APS, helping researchers to further clarify the pathogenesis of APS and find potential therapeutic targets, so as to achieve early diagnosis, early intervention, and ultimately improve the prognosis of patients.

This systematic review and meta-analysis were conducted to evaluate the cardiac and kidney-related adverse effects of roxadustat for the treatment of anemia in CKD patients. 18 trials with a total of 8806 participants were identified for analysis. We employed a fixed-effects model for analysis. The pooled result revealed no significant difference in the risk of occurrence of cardiac disorders when comparing CKD patients receiving roxadustat with the placebo (RR = 1.049; CI [0.918 to 1.200]) or ESA (RR = 1.066; CI [0.919 to 1.235]), in both dialysis-dependent (DD) (RR = 1.094; CI [0.925 to 1.293]) or non-dialysis-dependent (NDD) (RR = 1.036; CI [0.916 to 1.171]) CKD patients. No significant difference was observed in the risk of kidney-related adverse events when comparing roxadustat with the placebo (RR = 1.088; CI [0.980 to 1.209]) or ESA (RR = 0.968; CI [0.831 to 1.152]), in DD (RR = 2.649; CI [0.201 to 34.981]) or NDD (RR = 1.053; CI [0.965 to 1.149]) CKD patients. A high risk of hyperkalemia was observed in the roxadustat group in DD (RR = 0.939; CI [0.898 to 0.981]). Incidence of hypertension was higher in the roxadustat for NDD patients (RR = 1.198; CI [1.042 to 1.377]), or compared to the placebo (RR = 1.374; CI [1.153 to 1.638]). In summary, the risk of cardiac or kidney-related events observed in the roxadustat was not significantly increase whether in DD or NDD patients. However, attention must be paid to the occurrence of hyperkalemia for DD patients and hypertension in NDD patients using roxadustat.

Helicobacter pylori ( H. pylori ) is a globally widespread bacterial infection. Early diagnosis of this infection is vital for public and individual health. Prevalent diagnosis methods like the isotope 13 C or 14 C labelled urea breath test (UBT) are not convenient and may do harm to the human body. The use of cross-response gas sensor arrays (GSAs) is an alternative way for label-free detection of metabolite changes in exhaled breath (EB). However, conventional GSAs are complex to prepare, lack reliability, and fail to discriminate subtle changes in EB due to the use of numerous sensing elements and single dimensional signal. This work presents a dual-element multimodal GSA empowered with multimodal sensing signals including conductance ( G ), capacitance ( C ), and dissipation factor ( DF ) to improve the ability for gas recognition and H. pylori -infection diagnosis. Sensitized by poly(diallyldimethylammonium chloride) (PDDA) and the metal-organic framework material NH 2 -UiO66, the dual-element graphene oxide (GO)-composite GSAs exhibited a high specific surface area and abundant adsorption sites, resulting in high sensitivity, repeatability, and fast response/recovery speed in all three signals. The multimodal sensing signals with rich sensing features allowed the GSA to detect various physicochemical properties of gas analytes, such as charge transfer and polarization ability, enhancing the sensing capabilities for gas discrimination. The dual-element GSA could differentiate different typical standard gases and non-dehumidified EB samples, demonstrating the advantages in EB analysis. In a case-control clinical study on 52 clinical EB samples, the diagnosis model based on the multimodal GSA achieved an accuracy of 94.1%, a sensitivity of 100%, and a specificity of 90.9% for diagnosing H. pylori infection, offering a promising strategy for developing an accurate, non-invasive and label-free method for disease diagnosis.

Electrochemical co-reduction of nitrate (NO 3 - ) and carbon dioxide (CO 2 ) has been widely regarded as a promising route to produce urea under ambient conditions, however the yield rate of urea has remained limited. Here, we report an atomically ordered intermetallic pallium-zinc (PdZn) electrocatalyst comprising a high density of PdZn pairs for boosting urea electrosynthesis. It is found that Pd and Zn are responsible for the adsorption and activation of NO 3 - and CO 2 , respectively, and thus the co-adsorption and co-activation NO 3 - and CO 2 are achieved in ordered PdZn pairs. More importantly, the ordered and well-defined PdZn pairs provide a dual-site geometric structure conducive to the key C-N coupling with a low kinetical barrier, as demonstrated on both operando measurements and theoretical calculations. Consequently, the PdZn electrocatalyst displays excellent performance for the co-reduction to generate urea with a maximum urea Faradaic efficiency of 62.78% and a urea yield rate of 1274.42 μg mg -1  h -1 , and the latter is 1.5-fold larger than disordered pairs in PdZn alloys. This work paves new pathways to boost urea electrosynthesis via constructing ordered dual-metal pairs., (© 2024. The Author(s).)

Direct seawater splitting (DSS) offers an aspirational route toward green hydrogen (H 2 ) production but remains challenging when operating in a practically continuous manner, mainly due to the difficulty in establishing the water supply-consumption balance under the interference from impurity ions. A DSS system is reported for continuous ampere-level H 2 production by coupling a dual-cation exchange membrane (CEM) three-compartment architecture with a circulatory electrolyte design. Monovalent-selective CEMs decouple the transmembrane water migration from interferences of Mg 2+ , Ca 2+ , and Cl - ions while maintaining ionic neutrality during electrolysis; the self-loop concentrated alkaline electrolyte ensures the constant gradient of water chemical potential, allowing a specific water supply-consumption balance relationship in a seawater-electrolyte-H 2 sequence to be built among an expanded current range. Even paired with commercialized Ni foams, this electrolyzer (model size: 2 × 2 cm 2 ) continuously produces H 2 from flowing seawater with a rate of 7.5 mL min -1 at an industrially relevant current of 1.0 A over 100 h. More importantly, the energy consumption can be further reduced by coupling more efficient NiMo/NiFe foams (≈6.2 kWh Nm -3 H 2 at 1.0 A), demonstrating the potential to further optimize the continuous DSS electrolyzer for practical applications., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Wound management remains a great challenge for clinicians due to the complex physiological process of wound healing. Porous silicon (PSi) with controlled pore morphology, abundant surface chemistry, unique photonic properties, good biocompatibility, easy biodegradation and potential bioactivity represent an exciting class of materials for various biomedical applications. In this review, we focus on the recent progress of PSi in the design of advanced sensing and delivery systems for wound management applications. Firstly, we comprehensively introduce the common type, normal healing process, delaying factors and therapeutic drugs of wound healing. Subsequently, the typical fabrication, functionalization and key characteristics of PSi have been summarized because they provide the basis for further use as biosensing and delivery materials in wound management. Depending on these properties, the rise of PSi materials is evidenced by the examples in literature in recent years, which has emphasized the robust potential of PSi for wound monitoring, treatment and theranostics. Finally, challenges and opportunities for the future development of PSi-based sensors and delivery systems for wound management applications are proposed and summarized. We hope that this review will help readers to better understand current achievements and future prospects on PSi-based sensing and delivery systems for advanced wound management., (Copyright © 2024. Published by Elsevier B.V.)

To investigate the clinical application value of pharmacogenetic testing in individualized drug therapy for adult male patients with schizophrenia. A total of 186 adult patients with schizophrenia were enrolled and randomised into the pharmacogenetic (PGx) intervention group and the standard care group. In the PGx intervention group, PGx testing was performed, and the medication regimen was adjusted according to the results of the pharmacogenomic analysis. In contrast, in the standard care group, patients were treated according to the physician's medication experience. Differences in the primary indicator of schizophrenia, the Positive and Negative Symptom Scale (PANSS), and the secondary efficacy measures, the Clinical Global Impressions-Severity of Illness scale (CGI-SI) and Clinical Global Impressions-Global Improvement (CGI-GI) scale, were compared between the intervention and standard care groups. At baseline, the PGx intervention group consisted of 109 individuals, while the standard care group had 77 participants. After 12 weeks of treatment, 49 individuals withdrew from the PGx group (a dropout rate of 45.0%), and 34 withdrew from the standard care group (a dropout rate of 44.2%), with no significant difference in dropout rates between the two groups. The PANSS score reduction rate in the PGx intervention group significantly exceeded that of the standard care group during weeks 3, 6, and 12 of follow-up (P < 0.05). At the 12th week, the PGx intervention group achieved a treatment response rate of 81.7%, significantly surpassing the 48.8% of the standard care group (odds ratio of 4.67, 95% confidence interval of 1.96-11.41; P = 0.001). Furthermore, the PGx intervention was significantly more effective than standard care regardless of whether the patient had a first episode or a relapse (P < 0.05). Furthermore, the Global Assessment of Functioning (GAF) scores and the Personal and Social Performance Scale (PSP) score changes in the PGx intervention group were both significantly different from those in the standard care group (P < 0.05). It is noteworthy that the PGx intervention similarly improves the prognostic outcomes for patients with and without a family history of mental disorders. In conclusion, the application of a PGx intervention treatment model based on PGx testing can significantly improve medication efficacy and shorten the time to achieve the effects of medication in schizophrenia., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The introduction of battery-type cathode has been commonly considered a preferred approach to boost the energy density of aqueous hybrid energy storage devices (AHESDs) in alkalic systems, but AHESDs with both high energy density and power density are rare due to the great challenge in designing battery-type anode materials with high rate and durability comparable to capacitive-type carbon anodes. In this paper, a well-hydrated iron selenate (FeSeO) sheath is constructed around FeOOH nanorods by a facile electrochemical activation, demonstrating the unique multifunction in fasting charge diffusion, promoting the dissociation of H 2 O, and inhibiting the irreversible phase transition of FeOOH to inert γ-Fe 2 O 3 , which endow the hydrated sheath coated Fe-based anodes with an impressive rate capability and superior durability. Thanks to the comprehensive performance of this Fe-based anode, the assembled AHESD delivered a high energy density of 117 Wh kg -1 with the extraordinary durability of almost 100% capacity retention after 40 000 cycles. Even at an ultrahigh power density of 27 000 W kg -1 , an impressive energy density of 65 Wh kg -1 can be achieved, which rivals previously reported energy-storage devices., (© 2024 Wiley‐VCH GmbH.)

Autoimmune diseases are pathological autoimmune reactions in the body caused by various factors, which can lead to tissue damage and organ dysfunction. They can be divided into organ-specific and systemic autoimmune diseases. These diseases usually involve various body systems, including the blood, muscles, bones, joints and soft tissues. The transient receptor potential (TRP) and PIEZO receptors, which resulted in David Julius and Ardem Patapoutian winning the Nobel Prize in Physiology or Medicine in 2021, attracted people's attention. Most current studies on TRP and PIEZO receptors in autoimmune diseases have been carried out on animal model, only few clinical studies have been conducted. Therefore, this study aimed to review existing studies on TRP and PIEZO to understand the roles of these receptors in autoimmune diseases, which may help elucidate novel treatment strategies.

Inflammatory bowel disease (IBD) is a common disease of the digestive system, and an excessive immune response mediated by the nuclear factor κ-B (NF-κB) signaling pathway is an essential etiology. Recent studies have found that bovine milk exosomes can improve intestinal mucosal health by delivering microRNA (miRNA), but the mechanism of action is so far unknown. In the present study, we analyzed the differential expression profiles of miRNA in colostrum and mature milk exosomes using high-throughput sequencing, based on the demonstration that colostrum exosomes inhibit the lipopolysaccharide (LPS)-induced intestinal epithelial NF-κB inflammatory pathway better than mature milk exosomes. The bta-miR-30a-5p, which is specifically highly expressed in colostrum, was screened, and its predicted target gene TRAM was found to be closely related to the NF-κB signaling pathway by functional enrichment analysis. Further, we used gene overexpression and silencing techniques and found that the bta-miR-30a-5p transfection treatment was confirmed to inhibit LPS-induced NF-κB signaling pathway activation and downstream pro-inflammatory factor expression, while the expression of its potential target gene, TRAM, was also suppressed. It is hypothesized that the high expression of bta-miR-30a-5p in colostrum, which targets TRAM to inhibit the downstream NF-κB inflammatory pathway, may be one of the molecular mechanisms responsible for its superior effect on resisting inflammatory attack compared to mature milk.

Podocan, the fifth member of Small Leucine-Rich Proteoglycan (SLRP) family of extracellular matrix components, is poorly known in muscle development. Previous studies have shown that Podocan promotes C2C12 differentiation in mice. In this study, we elucidated the effect of Podocan on skeletal muscle post-injury regeneration and its underlying mechanism. Injection of Podocan protein promoted the process of mice skeletal muscle post-injury regeneration. This effect seemed to be from the acceleration of muscle satellite cell differentiation in vivo. Meanwhile, Podocan promoted myogenic differentiation in vitro by binding with TGF-β1 to inhibit the activity of the TGF-β signaling pathway. These results indicated that Podocan had the potential roles to enhance skeletal muscle post-injury regeneration. Its mechanism is likely the regulation of the expression of p-Smad2 and p-Smad4 related to the TGF-β signaling pathway by interacting with TGF-β1., (© 2024 Federation of American Societies for Experimental Biology.)

Aqueous sodium-ion batteries are known for poor rechargeability because of the competitive water decomposition reactions and the high electrode solubility. Improvements have been reported by salt-concentrated and organic-hybridized electrolyte designs, however, at the expense of cost and safety. Here, we report the prolonged cycling of ASIBs in routine dilute electrolytes by employing artificial electrode coatings consisting of NaX zeolite and NaOH-neutralized perfluorinated sulfonic polymer. The as-formed composite interphase exhibits a molecular-sieving effect jointly played by zeolite channels and size-shrunken ionic domains in the polymer matrix, which enables high rejection of hydrated Na + ions while allowing fast dehydrated Na + permeance. Applying this coating to electrode surfaces expands the electrochemical window of a practically feasible 2 mol kg -1 sodium trifluoromethanesulfonate aqueous electrolyte to 2.70 V and affords Na 2 MnFe(CN) 6 //NaTi 2 (PO 4 ) 3 full cells with an unprecedented cycling stability of 94.9% capacity retention after 200 cycles at 1 C. Combined with emerging electrolyte modifications, this molecular-sieving interphase brings amplified benefits in long-term operation of ASIBs., (© 2024. The Author(s).)

Ulcerative colitis (UC) is a chronic gastrointestinal disease that can be managed with 5-aminosalicylic acid (5-ASA), the standard treatment for UC. However, the effectiveness of 5-ASA is not always optimal. Our study revealed that despite 5-ASA treatment, cells continued to experience excessive ferroptosis, which may hinder mucosal healing in UC and limit the success of this treatment approach in achieving disease remission. We found that combining 5-ASA with the ferroptosis inhibitor Fer-1 led to a significant inhibition of ferroptosis in macrophages present in the colon tissue, along with an increase in the proportion of M2 macrophages, suggesting that targeting ferroptosis in M2 macrophages could be a potential therapeutic strategy for alleviating UC. Our study also demonstrated that M2 macrophages are more susceptible to ferroptosis compared to M1 macrophages, and this susceptibility is associated with the activated arachidonic acid (AA) metabolism pathway mediated by ERK-cPLA2-ACSL4. Additionally, we found that the expression of cPLA2 gene pla2g4a was increased in the colon of UC patients compared to healthy controls. Furthermore, targeted metabolomics analysis revealed that the combination treatment group, as opposed to the 5-ASA treatment group, exhibited the ability to modulate AA metabolism. Overall, our findings emphasize the importance of addressing macrophage ferroptosis in order to enhance macrophage anti-inflammation, improve mucosal healing, and achieve better therapeutic outcomes for patients with UC., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the association of timing, frequency, and food quality of night eating with all-cause, cancer, and diabetes mortality., Methods: This study included 41,744 participants from the US National Health and Nutrition Examination Survey (2002-2018). Night eating information was collected by 24-h dietary recall and the exposures were timing, frequency, and food quality of night eating. Food quality was assessed by latent class analysis. The outcomes were all-cause, cancer, and diabetes mortality, which were identified by the National Death Index and the International Classification of Diseases 10th Revision. Adjusted hazard ratios [aHR] with 95% confidence intervals [CI] were computed by Cox regression., Results: During a median follow-up of 8.7 years, 6066 deaths were documented, including 1381 from cancer and 206 from diabetes. Compared with no night eating (eating before 22:00), the later timing of night eating was associated with higher risk of all-cause and diabetes mortality (each P-trend <0.05) rather than cancer mortality, with the highest risk of eating being 00:00-1:00 (aHR 1.38, 95% CI 1.02-1.88) and being 23:00-00:00 (aHR 2.31, 95% CI 1.21-4.40), respectively. However, the increased risks were not observed for 22:00-23:00. Likewise, one time or over frequency of night eating was associated with higher all-cause and diabetes mortality (each P < 0.05). That risks were further observed in high-dietary-energy-density group of night eating (all-cause mortality: aHR 1.21 [95% CI 1.06-1.38]; diabetes mortality: aHR 1.97 [95% CI 1.13-3.45]), but not in low-dietary-energy-density group. Finally, correlation analysis found positive associations of night eating with glycohemoglobin, fasting glucose, and OGTT., Conclusions: Night eating was associated with increased all-cause, cancer and diabetes mortality; however, reduction of excess mortality risk was observed when eating before 23:00 or low-dietary-energy-density foods., (© 2024. The Author(s).)

Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy. Antibodies binding to complexes of platelet factor 4 (PF4) and heparin is the trigger of HIT. A method using size exclusion chromatography with multi-angle laser light scattering detector (SEC-MALS) was developed in this work. The soluble ultra-large complex (ULC) was separated from the small complex (SC) and their molecular weights (MWs) were firstly measured. The complexes of PF4 and three heparins with different MW, including unfractionated heparin (UFH), dalteparin (Daltep) and enoxaparin (Eno) were characterized using this method. The contents and the sizes of ULC increased gradually when heparins were added to PF4 to certain amounts. While, they reduced after more heparins were added. It is the first time to measure the MWs of the biggest ULC of PF4-heparins as millions of Dalton. at the proper ratios of PF4 to heparin (PHR). Meanwhile, those mixtures at those certain PHRs induced the higher expression of CD83 and CD14 markers on dendritic cells (DCs) suggesting that they had stronger immunogenicity and is critical for HIT., 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.)

Autoimmune hepatitis (AIH) is a progressive liver disease mediated by the immune system that involves an imbalance in pro-inflammatory and regulatory mechanisms including regulatory T cells (Tregs), T helper 17 (Th17) cells, Th1, macrophages, and many other immune cells. Current steroid therapy for AIH has significant systemic side effects and is poorly tolerated by some individuals. Therefore, there is an urgent need for alternative treatments. Maintaining homeostasis in macrophage differentiation and activation is crucial for regulating immune responses in hepatitis. In this study, we loaded small interfering RNA (siRNA) targeting receptor-interacting protein kinase 3 (RIPK3) into M2-type macrophage-derived exosomes (M2 Exos) to create functionalized exosomes called M2 Exos/siRIPK3. These exosomes demonstrated a natural ability to target the liver in mice, as they were efficiently taken up by hepatic macrophages and showed significant and stable accumulation. M2 Exos/siRIPK3 effectively mitigated immune-mediated hepatitis by suppressing the expression of RIPK3, resulting in a reduced release of pro-inflammatory cytokines and chemokines in both liver tissues and serum. Additionally, M2 Exos/siRIPK3 exhibited immunomodulatory effects, as its administration resulted in a decreased proportion of hepatic and splenic Th17 cells, along with an increased ratio of Tregs. Overall, this study suggests that loading small molecule drugs onto M2 Exos could be a promising approach for developing immunomodulators that specifically target liver macrophages to treat AIH. This strategy has the potential to provide a safer and more effective alternative to current therapy for AIH patients., 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 Masson SAS.. All rights reserved.)

Purpose: We investigate the association of HTR1A rs10042486 and rs6295 with efficacy and plasma concentrations of atypical antipsychotics in the treatment of male patients with schizophrenia., Patients and Methods: A total of 140 male patients diagnosed with schizophrenia who were treated with any single atypical antipsychotic between May 2020 and May 2022 were retrospectively included. Clinical symptoms were assessed using Positive and Negative Syndrome Scale (PANSS). All SNPs were typed using Agena Bioscience MassARRAY DNA mass spectrometry. Plasma concentrations of antipsychotics at week 3, 6 and 12 after treatment commence were analyzed using mass spectrometry., Results: For efficacy of atypical antipsychotics, we observed no significant difference between HTR1A rs10042486, rs6295 and positive symptom improvement, where the patients with heterozygous mutant at the rs10042486 and rs6295 locus were superior to those with wild-type or homozygous mutant genotypes on negative symptom improvement, especially at 12 weeks of follow-up when the difference between genotypes at the rs6295 locus have statistical significance ( P = 0.037). For plasma concentration, we found that quetiapine plasma concentrations were significantly lower in patients with mutation-heterozygous types than in wild-type and homozygous mutation genotypes at week 6. In contrast, higher plasma concentrations were found for mutant heterozygous than wild genotypes in the risperidone monotherapy analysis, and the difference among genotypes at the rs6295 locus was statistically significant at 6 weeks of follow-up., Conclusion: The assessment of the correlation of genetic polymorphisms of HTR1A rs6295 and rs10042486 in male patients with schizophrenia with the monitoring of therapeutic drug concentrations and therapeutic efficacy provides a constructive foundation for the clinical individualization of antipsychotics, such as quetiapine and risperidone, which is important in selecting the dose of the medication and improving the improvement of negative symptoms., Competing Interests: Jingfeng Tong and Chengchen Huang are affiliated with Shanghai Conlight Medical Co., Ltd. The authors declare no other conflicts of interest in this work., (© 2024 Qin et al.)

Enzymatic mineralization is an advanced mineralization method that is often used to enhance the stiffness and strength of hydrogels, but often accompanied by brittle behavior. Moreover, the hydrogel systems with dense networks currently used for enzymatic mineralization are not ideal materials for bone repair applications. To address these issues, two usual bone repair hydrogels, poly(vinyl alcohol) (PVA) and sodium alginate (SA), were selected to form a double-network structure through repeated freeze-thawing and ionic cross-linking, followed by enzyme mineralization. The results demonstrated that both enzymatic mineralization and double-network structure improved the mechanical and biological properties and even exhibited synergistic effects. The mineralized PVASA hydrogels exhibited superior comprehensive mechanical properties, with a Young's modulus of 1.03 MPa, a storage modulus of 103 kPa, and an equilibrium swelling ratio of 132%. In particular, the PVASA hydrogel did not suffer toughness loss after mineralization, with a high toughness value of 1.86 MJ/m 3 . The prepared hydrogels also exhibited superior biocompatibility with a cell spreading area about 13 times that of mineralized PVA. It also effectively promoted cellular osteogenic differentiation in vitro and further promoted the formation of new bone in the femur defect region in vivo. Overall, the enzyme-mineralized PVASA hydrogel demonstrated combined strength and toughness and great potential for bone tissue engineering applications.

Colorectal cancer (CRC) is one of the most prevalent and deadly malignancies that can be influenced by Fusobacterium nucleatum (Fn), a bacterium that promotes tumor development and chemoresistance, resulting in limited therapeutic efficacy. Traditional antibiotics cannot effectively eliminate Fn at tumor site due to issues like biofilm formation, while chemotherapy alone fails to suppress tumor progression. Therefore, the development of new methods to eliminate Fn and promote antitumor efficacy is of great significance for improving the outcome of CRC treatment. Herein, we developed a nanodrug (OPPL) that integrates oleic acid-modified superparamagnetic iron oxide nanoparticles (O-SPIONs) and an amphiphilic polymer (PPL) to deliver the platinum prodrug and antimicrobial lauric acid (LA) for enhancing the treatment of CRC. We demonstrated that OPPL can synergistically enhance antibacterial and biofilm disruption activities against Fn along with the antimicrobial LA by producing reactive oxygen species (ROS) through its peroxidase-like activity. Furthermore, the OPPL nanodrug can increase intracellular ROS, promote lipid peroxides and deplete glutathione, leading to ferroptosis. By combining chemotherapy and induced ferroptosis, the OPPL nanodrug exhibited high cytotoxicity against CRC cells. In vivo studies showed that the OPPL nanodrug could enhance tumor accumulation, enable magnetic resonance imaging, suppresse tumor growth, and inhibit growth of intratumor Fn. These results suggest that OPPL is an effective and promising candidate for the treatment of Fn-infected CRC. STATEMENT OF SIGNIFICANCE: The enrichment of Fusobacterium nucleatum (Fn) in colorectal cancer is reported to exacerbate tumor malignancy and is particularly responsible for chemoresistance. To this respect, we strategically elaborated multifaceted therapeutics, namely OPPL nanodrug, combining oleic acid-modified superparamagnetic iron oxide nanoparticles (O-SPIONs) with a polymer containing a platinum prodrug and antimicrobial lauric acid. The O-SPION components exert distinctive peroxidase-like activity, capable of stimulating Fenton reactions selectively in the tumor microenvironment, consequently accounting for the progressive production of reactive oxygen species. Hence, O-SPIONs have been demonstrated to not only supplement the antimicrobial activities of lauric acid in overcoming Fn-induced chemoresistance but also stimulate potent tumor ferroptosis. Our proposed dual antimicrobial and chemotherapeutic nanodrug provides an appreciable strategy for managing challenging Fn-infected colorectal cancer., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In recent years, the incidence of intestinal ischemia-reperfusion injury (II/RI), inflammatory bowel disease (IBD), and colorectal cancer (CRC) has been gradually increasing, posing significant threats to human health. Autophagy and endoplasmic reticulum stress (ERS) play important roles in II/RI. Damage caused by ischemia and cellular stress can activate ERS, which in turn initiates autophagy to clear damaged organelles and abnormal proteins, thereby alleviating ERS and maintaining the intestinal environment. In IBD, chronic inflammation damages intestinal tissues and activates autophagy and ERS. Autophagy is initiated by upregulating ATG genes and downregulating factors that inhibit autophagy, thereby clearing abnormal proteins, damaged organelles, and bacteria. Simultaneously, persistent inflammatory stimulation can also trigger ERS, leading to protein imbalance and abnormal folding in the ER lumen. The activation of ERS can maintain cellular homeostasis by initiating the autophagy process, thereby reducing inflammatory responses and cell apoptosis in the intestine. In CRC, excessive cell proliferation and protein synthesis lead to increased ERS. The activation of ERS, regulated by signaling pathways such as IRE1α and PERK, can initiate autophagy to clear abnormal proteins and damaged organelles, thereby reducing the negative effects of ERS. It can be seen that autophagy and ERS play a crucial regulatory role in the development of intestinal diseases. Therefore, the progress in targeted therapy for intestinal diseases based on autophagy and ERS provides novel strategies for managing intestinal diseases. In this paper, we review the advances in regulation of autophagy and ERS in intestinal diseases, emphasizing the potential molecular mechanisms for therapeutic applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Stem cell tissue engineering is a potential treatment for osteoarthritis. However, the number of stem cells that can be delivered, loss of stem cells during injection, and migration ability of stem cells limit applications of traditional stem cell tissue engineering. Herein, kartogenin (KGN)-loaded poly(lactic-co-glycolic acid) (PLGA) porous microspheres is first engineered via emulsification, and then anchored with chitosan through the amidation reaction to develop a new porous microsphere (PLGA-CS@KGN) as a stem cell expansion vector. Following 3D co-culture of the PLGA-CS@KGN carrier with mesenchymal stem cells (MSCs), the delivery system is injected into the capsule cavity in situ. In vivo and in vitro experiments show that PLGA-CS microspheres have a high cell-carrying capacity up to 1 × 10 4 mm -3 and provide effective protection of MSCs to promote their controlled release in the osteoarthritis microenvironment. Simultaneously, KGN loaded inside the microspheres effectively cooperated with PLGA-CS to induce MSCs to differentiate into chondrocytes. Overall, these findings indicate that PLGA-CS@KGN microspheres held high cell-loading ability, adapt to the migration and expansion of cells, and promote MSCs to express markers associated with cartilage repair. Thus, PLGA-CS@KGN can be used as a potential stem cell carrier for enhancing stem cell therapy in osteoarthritis treatment., (© 2023 Wiley-VCH GmbH.)

Aqueous zinc-ion batteries (AZIBs) assembled with gel polymer electrolyte (GPE) have gained great popularity due to their low cost and safety. Nevertheless, the extensive utilization of GPE based AZIBs is hindered by various challenges, such as inadequate conductivity, limited mechanical strength, and unstable electrochemical properties. Herein, through the multiple cross-linking reaction of sodium alginate (SA), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP) and graphene oxide (GO), a hydrated GPE with high conductivity and excellent mechanical property was prepared. GO formed strong hydrogen-bonding interaction with polymers to build a three-dimensional network structure for ion migration and improved the mechanical property of GPE. The prepared GPE showed high ionic conductivity of 2.89×10 -3  S cm -1 and excellent tensile strength of 900 kPa. In addition, the assembled Zn-Li hybrid battery provided a discharge specific capacity retention rate of 67.6 % and a Coulombic efficiency (CE) of approximate 100 % after 1000 cycles at 1 C., (© 2023 Wiley-VCH GmbH.)

In the present study, the influence of viscosity on the fermentation characteristics of fructooligosaccharides (FOS) by gut microbiota was examined. Different concentrations of methylcellulose (MC) were added to create varying viscosities and the mixture was fermented with FOS by gut microbiota. The results demonstrated that higher viscosity had a significant impact on slowing down the fermentation rate of FOS. Specifically, the addition of 2.5 wt% MC, which had the highest viscosity, resulted in the lowest and slowest production of gas and short-chain fatty acids (SCFAs), indicating that increased viscosity could hinder the breakdown of FOS by gut microbiota. Additionally, the slower fermentation of FOS did not significantly alter the structure of the gut microbiota community compared to that of FOS alone, suggesting that MC could be used in combination with FOS to achieve similar prebiotic effects and promote gut health while exhibiting a slower fermentation rate.

Objective: The pathogenesis, diagnosis, and treatment of Sjögren's syndrome (SS) face many challenges, and there is an urgent need to develop new technologies to improve our understanding of SS., Methods: By searching the literature published domestically and internationally in the past 20 years, this artical reviewed the research of various omics techniques in SS., Results: Omics technology provided valuable insights into the pathogenesis, early diagnosis, condition and efficacy evaluation of SS. It is helpful to reveal the pathogenesis of the disease and explore new treatment schemes, which will open a new era for the study of SS., Conclusion: At present, omics research has made some gratifying achievements, but there are still many uncertainties. Therefore, in the future, we should improve research techniques, standardize the collection of samples, and adopt a combination of multi-omics techniques to jointly study the pathogenesis of SS and provide new schemes for its treatment., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Hydrogel electrolytes hold great promise in developing flexible and safe batteries, but the presence of free solvent water makes battery chemistries constrained by H 2 evolution and electrode dissolution. Although maximizing salt concentration is recognized as an effective strategy to reduce water activity, the protic polymer matrices in classical hydrogels are occupied with hydrogen-bonding and barely involved in the salt dissolution, which sets limitations on realizing stable salt-concentrated environments before polymer-salt phase separation occurs. Inspired by the role of protein methylation in regulating intracellular phase separation, here we transform the "inert" protic polymer skeletons into aprotic ones through methylation modification to weaken the hydrogen-bonding, which releases free hydrogen bond acceptors as Lewis base sites to participate in cation solvation and thus assist salt dissolution. An unconventionally salt-concentrated hydrogel electrolyte reaching a salt fraction up to 44 mol % while retaining a high Na + /H 2 O molar ratio of 1.0 is achieved without phase separation. Almost all water molecules are confined in the solvation shell of Na + with depressed activity and mobility, which addresses water-induced parasitic reactions that limit the practical rechargeability of aqueous sodium-ion batteries. The assembled Na 3 V 2 (PO 4 ) 3 //NaTi 2 (PO 4 ) 3 cell maintains 82.8 % capacity after 580 cycles, which is the longest cycle life reported to date., (© 2023 Wiley-VCH GmbH.)

Objective . There has been a considerable amount of computer-aided diagnosis (CAD) methods highlighted in the field of ultrasonic examination (USE) of thyroid nodules. However, few researches focused on the automatic risk classification, which was the basis for determining whether fine needle aspiration (FNA) was needed. The aim of this work was to implement automatic risk level assessment of thyroid nodules. Approach . Firstly, 1862 cases of thyroid nodules with the results of USE and FNA were collected as the dataset. Then, an improved U-Net++ model was utilized for segmenting thyroid nodules in ultrasound images automatically. Finally, the segmentation result was imported into a multi-task convolutional neural network (MT-CNN), the design of which was based on the clinical guideline called KWAK TI-RADS. Apart from the category of benign and malignant, the MT-CNN also exported the classification result of four malignant features, solid component (SC), hypoechogenicity or marked hypoechogenicity (HMH), microlobulated or irregular margin (MIM), microcalcification (MC), which were used for counting the risk level in KWAK TI-RADS. Main results . The performance of the improved U-Net++ was evaluated on our test set, including 302 cases. The Dice coefficient and intersection over union reached 0.899, 0.816, respectively. The classification accuracy rates of SC, HMH, MIM, MC, were 94.5%, 92.8%, 86.1%, 88.9%, while the false positive (FP) rate was 6.0%, 5.6%, 10.6%, 12.9% respectively. As for the category of benign and malignant, the precision and recall rates were 93.7% and 94.4%. Significance . The proposed CAD method showed favourable performance in the diagnosis of thyroid nodules. Compared with other methods, it could provide reports closer to clinical practice for doctors., (© 2023 Institute of Physics and Engineering in Medicine.)

Learning in virtual museum can transcend the limits of time and space. The virtual museum that combines expertise in different disciplines provides a virtual learning environment for college students, but how to intervene in museum learning has been unclear. Targeted at this question, this study selected 2030 majors in clinical medicine from a certain university and the final results exhibited four types of learners who are of high, medium, low and absent museum immersion, respectively. When the learners visited the virtual museum, their behavior data were collected backstage and later used as data source. The method of fuzzy c clustering analysis was utilized to test the behavior recognition results of virtual museum learning, and lag sequential analysis (LSA) was used to carry out sequential transformation of learning behaviors in virtual museum. In this study, the four types of learners were subsumed under two broad categories of middle & high museum immersion and low & absent museum immersion. The importance of behavior was identified with random forest algorithm, and the intervention mechanism of museum teaching was designed according to the analysis results. Specifically, such strategies as museum support, voice guidance, video guidance, sub-museum ordering, rewards points on the list, etc. were used to study the museum learners in need of intervention. The results showed that the learning state of some learners was significantly improved., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wu 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.)

Objective: The prognosis for gastric cancer (GC), a prevalent tumor of the digestive system, is unfavorable. The involvement of glutathione peroxidase 3 (GPX3) in tumorigenesis is significant, yet its specific role in GC remains insufficiently investigated. Thus, the aim of this study was to determine the potential impact of GPX3 on GC and elucidate the underlying mechanism. Methods: The expression and survival of GPX3 in GC were analyzed using TCGA data. Additionally, the GPX3 mRNA and protein levels in GC were also assessed using datasets from GTEx, GEPIA, and HPA. A total of 38 pairs of GC tissues, along with their adjacent normal tissues, were collected from the Tianjin Medical University General Hospital, accompanied by detailed clinical information. The expression levels of GPX3 were subsequently determined for the purpose of validation. Following expression, correlation, and survival analyses, we proceeded to investigate the upstream non-coding RNA (ncRNA) of GPX3 using starBase and miRNet. Additionally, the co-expression networks of GPX3 were examined based on LinkedOmics. Lastly, we explored the correlation between GPX3 and immune cell infiltration, as well as the biomarkers of immune cells and immune checkpoints in GC. Furthermore, the GDSC database offered valuable drug sensitivity information. Results: A lower expression of GPX3 was observed in individuals with GC, while a higher expression of GPX3 was associated with a poorer prognosis. The DUBR/hsa-miR-502-3p/GPX3 pathway was identified as the most promising upstream ncRNA pathway related to GPX3 in GC. GO and KEGG enrichment analysis revealed that GPX3 expression was linked to coagulation cascades and cell locomotion. Furthermore, GPX3 levels in GC were positively correlated with immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. The group with low GPX3 expression also exhibited increased sensitivity to 5-fluorouracil, doxorubicin, and other drugs. Conclusions: Collectively, we hypothesized that the potential involvement of non-coding RNAs in the downregulation of GPX3 could contribute to the inhibition of tumor formation during the malignant transition from gastritis to GC. Nevertheless, it was plausible that GPX3 may also facilitate tumor progression to advanced stages by promoting immune cell infiltration and activating immune checkpoints., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Primary Sjögren's syndrome (pSS) is an autoimmune disease that leads to the destruction of exocrine glands and multisystem lesions. Abnormal proliferation, apoptosis, and differentiation of CD4 + T cells are key factors in the pathogenesis of pSS. Autophagy is one of the important mechanisms to maintain immune homeostasis and function of CD4 + T cells. Human umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) may simulate the immunoregulation of MSCs while avoiding the risks of MSCs treatment. However, whether UCMSC-Exos can regulate the functions of CD4 + T cells in pSS, and whether the effects via the autophagy pathway remains unclear., Methods: The study analyzed retrospectively the peripheral blood lymphocyte subsets in pSS patients, and explored the relationship between lymphocyte subsets and disease activity. Next, peripheral blood CD4 + T cells were sorted using immunomagnetic beads. The proliferation, apoptosis, differentiation, and inflammatory factors of CD4 + T cells were determined using flow cytometry. Autophagosomes of CD4 + T cells were detected using transmission electron microscopy, autophagy-related proteins and genes were detected using western blotting or RT-qPCR., Results: The study demonstrated that the peripheral blood CD4 + T cells decreased in pSS patients, and negatively correlated with disease activity. UCMSC-Exos inhibited excessive proliferation and apoptosis of CD4 + T cells in pSS patients, blocked them in the G0/G1 phase, inhibited them from entering the S phase, reduced the Th17 cell ratio, elevated the Treg ratio, inhibited IFN-γ, TNF-α, IL-6, IL-17A, and IL-17F secretion, and promoted IL-10 and TGF-β secretion. UCMSC-Exos reduced the elevated autophagy levels in the peripheral blood CD4 + T cells of patients with pSS. Furthermore, UCMSC-Exos regulated CD4 + T cell proliferation and early apoptosis, inhibited Th17 cell differentiation, promoted Treg cell differentiation, and restored the Th17/Treg balance in pSS patients through the autophagy pathway., Conclusions: The study indicated that UCMSC-Exos exerts an immunomodulatory effect on the CD4 + T cells, and maybe as a new treatment for pSS., (© 2023. The Author(s).)

Cadmium (Cd) is a highly toxic heavy metal with severe impacts on plant growth and development. Although a multitude of plants have acquired strong tolerance to Cd stress, the underlying molecular mechanism has not been fully elucidated. Here, we identified a Agamous-like MADS-box gene (EcAGL) from Erigeron canadensis. The expression of EcAGL was obviously raised under Cd stress and subcellular localization indicated EcAGL was localized in the nucleus. Overexpression of EcAGL in Arabidopsis thaliana showed marked alleviation of the Cd-induced reduction; Compared to wild-type lines, the antioxidant enzymes activities were increased in EcAGL overexpressing lines under Cd stress. The roots Cd content of transgenic lines was not different with the control plants, whereas significant reduction in shoots Cd content was detected in the transgenic lines, indicating that this gene can enhance Cd tolerance by reducing Cd accumulation in Arabidopsis. Moreover, the expression levels of heavy metal ATPase (AtHMA2 and AtHMA3) and natural resistance-associated macrophage protein (AtNRAMP5) genes in the root of transgenic lines decreased under Cd stress, indicating that EcAGL likely hampered the Cd transport pathway. Gene expression profiles in shoot showed that EcAGL likely modulates the expression of 1-aminocyclopropane-1-carboxylic acid synthase gene (AtACS2), which is involved in the ethylene synthesis pathway, to strengthen the tolerance to Cd. Collectively, these results indicate that EcAGL plays a significant role in regulating Cd tolerance in E. canadensis by alleviating oxidative stress, Cd transport and affecting the ethylene biosynthesis pathway, providing new insight into the molecular mechanism underlying plant tolerance to Cd stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction: The relationship between oral and gut microbiota in alcohol dependence (AD) is not well understood, particularly the effects of oral microbiota on the intestinal microbiota. The current study aimed to explore the association between oral and gut microbiota in AD to clarify whether oral microbiota could ectopically colonize into the gut., Methods: 16S rRNA sequence libraries were used to compare oral and gut microbial profiles in persons with AD and healthy controls (HC). Source Tracker and NetShift were used to identify bacteria responsible for ectopic colonization and indicate the driver function of ectopic colonization bacteria., Results: The α-diversity of oral microbiota and intestinal microbiota was significantly decreased in persons with AD (all p < 0.05). Principal coordinate analysis indicated greater similarity between oral and gut microbiota in persons with AD than that in HC, and oral-gut overlaps in microbiota were found for 9 genera in persons with AD relative to only 3 genera in HC. The contribution ratio of oral microbiota to intestinal microbiota composition in AD is 5.26% based on Source Tracker，and the AD with ectopic colonization showed the daily maximum standard drinks, red blood cell counts, hemoglobin content, and PACS scores decreasing (all p < 0.05)., Discussion: Results highlight the connection between oral-gut microbiota in AD and suggest novel potential mechanistic possibilities., 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 Hu, Ni, Zhao, Li, Gao, Kang, Yu, Qin, Zhao, Peng, Lu and Sun.)

Reactive oxygen species (ROS)-sensitive theranostics hold great promise for personalized treatment of various diseases. However, most current theranostics rely on luminescence techniques with complex probe design, high background signals and bulky instruments. Herein, we propose a novel thermal signal-based theranostic for ROS monitoring by detecting the photothermal signal change of near-infrared (NIR)-active dye (IR820) that released from the porous silicon (PSi)-based carrier and demonstrate its application for synergistic theranostics of chronic wounds. Owing to the reduced energy level caused by J-aggregate formation and the improved non-radiative decay pathway, trapping of IR820 in calcium ion sealed PSi (I-CaPSi) exhibits significantly enhanced photothermal capability compared to free IR820. With the degradation of PSi induced by ROS, the trapped and aggregated IR820 is released to be dispersed and free state. Therefore, the decrease of photothermal signal in response to ROS stimuli can be recorded in real time. Using a portable smartphone equipped with a thermal camera, ROS levels at wounds can be monitored non-invasively and conveniently to indicate exacerbation or healing conditions. Moreover, the NIR-triggered smart delivery platform also triggers photothermal and photodynamic therapy to inhibit bacterial growth and exhibits bioactivity to promote cell migration and angiogenesis via the Si ions released from PSi. With the synergistic advantages of ROS-responsive property, pro-healing ability, anti-infection effect and excellent biosafety, the NIR-activated theranostic platform achieves convenient diagnosis and effective treatment in diabetic wound infection models in vivo. Overall, this work demonstrates a promising paradigm of I-CaPSi smart delivery platform with great clinical translation potential for home-based chronic wound theranostics., Competing Interests: Declaration of Competing Interest The author declare no competing financial interest., (Copyright © 2023. Published by Elsevier B.V.)

With increasing health awareness worldwide, lactose intolerance has become a major concern of consumers, creating new market opportunities for low-lactose/lactose-free dairy foods. In recent years, through innovating processes and technologies, dairy manufacturers have significantly improved the variety, and functional and sensory qualities of low-lactose and lactose-free dairy products. Based on this, this paper first covers the pathology and epidemiology of lactose intolerance and market trends. Then, we focus on current advantages and disadvantages of different lactose hydrolysis technologies and improvements in these technologies to enhance nutritional value, and functional, sensory, and quality properties of lactose-free dairy products. We found that more and more cutting-edge technologies are being applied to the production of lactose-free dairy products, and that these technologies greatly improve the quality and production efficiency of lactose-free dairy products. Hopefully, our review can provide a theoretical basis for the marketing expansion and consumption guidance for low-lactose/lactose-free dairy products.

Dual-ion batteries involving anion intercalation into graphite cathodes represent promising battery technologies for low-cost and high-power energy storage. However, the fundamental origins regarding much lower capacities of graphite cathodes in earth abundant and inexpensive multivalent electrolytes than in Li-ion electrolytes remain elusive. Herein, we reveal that the limited anion-storage capacity of a graphite cathode in multivalent electrolytes is rooted in the abnormal multivalent-cation co-intercalation with anions in the form of large-sized anionic complexes. This cation co-intercalation behavior persists throughout the stage evolution of graphite intercalation compounds and leads to a significant decrease of sites practically viable for capacity contribution inside graphite galleries. Further systematic studies illustrate that the phenomenon of cation co-intercalation into graphite is closely related to the high energy penalty of interfacial anion desolvation due to the strong cation-anion association prevalent in multivalent electrolytes. Leveraging this understanding, we verify that promoting ionic dissociation in multivalent electrolytes by employing high-permittivity and oxidation-tolerant co-solvents is effective in suppressing multivalent-cation co-intercalation and thus achieving increased capacity of graphite cathodes. For instance, introducing adiponitrile as a co-solvent to a Mg 2+ -based carbonate electrolyte leads to 83% less Mg 2+ co-intercalation and a ∼29.5% increase in delivered capacity of the graphite cathode.

Aims: To investigate the involvement of serotonin transporter (SERT) in colonic epithelial cells in the anti-osteoporosis role of Lactobacillus acidophilus (LA) supernatant (LAS). Methods: The abundance of fecal LA and bone mineral density (BMD) in patients with osteoporosis (OP) or severe osteoporosis were assessed. The protective role of LA in osteoporosis and the expression of SERT and relative signaling were evaluated. Results: Abundance of fecal LA was decreased in patients with severe OP and was positively correlated with BMD. Supplementing LAS to mice alleviated senile osteoporosis. In vitro , NOD2/RIP2/NF-κB signaling was inhibited by LAS due to increased SERT expression. Conclusion: LAS alleviates OP in mice by producing protective metabolites and upregulating SERT expression and represents a promising therapeutic agent.

Direct and nondestructive assessment of material properties of skeletal muscle in vivo shall advance our understanding of intact muscle mechanics and facilitate personalized interventions. However, this is challenged by intricate hierarchical microstructure of the skeletal muscle. We have previously regarded the skeletal muscle as a composite of myofibers and extracellular matrix (ECM), formulated shear wave propagation in the undeformed muscle using the acoustoelastic theory, and preliminarily demonstrated that ultrasound-based shear wave elastography (SWE) could estimate microstructure-related material parameters (MRMPs): myofiber stiffness μ f , ECM stiffness μ m , and myofiber volume ratio V f . The proposed method warrants further validation but is hampered by the lack of ground truth values of MRMPs. In this study, we presented analytical and experimental validations of the proposed method using finite-element (FE) simulations and 3D-printed hydrogel phantoms, respectively. Three combinations of different physiologically relevant MRMPs were used in the FE simulations where shear wave propagations in the corresponding composite media were simulated. Two 3D-printed hydrogel phantoms with the MRMPs close to those of a real skeletal muscle (i.e., μ f =2.02kPa, μ m =52.42kPa, and V f =0.675,0.832) for ultrasound imaging were fabricated by an alginate-based hydrogel printing protocol that we modified and optimized from the freeform reversible embedding of suspended hydrogels (FRESH) method in literature. Average percent errors of (μ f ,μ m ,V f ) estimates were found to be (2.7%,7.3%,2.4%)in silico and (3.0%,8.0%,9.9%)in vitro. This quantitative study corroborated the potential of our proposed theoretical model along with ultrasound SWE for uncovering microstructural characteristics of the skeletal muscle in an entirely nondestructive way., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)