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The medical metaverse is a combination of medicine, computer science, information technology and other cutting-edge technologies. It redefines the method of information interaction about doctor-patient communication, medical education and research through the integration of medical data, knowledge and services in a virtual environment. Artificial intelligence (AI) is a discipline that uses computer technology to study and develop human intelligence. AI has infiltrated every aspect of medical metaverse and is deeply integrated with the technologies that build medical metaverse, such as large language models (LLMs), digital twins, blockchain and extended reality (including VR/AR/XR). AI has become an integral part of the medical metaverse building process. Moreover, AI also provides richer medical metaverse functions, including diagnosis, education, and consulting. This paper aims to introduce how AI supports the development of medical metaverse, including its specific application scenarios, shortcomings and future development. Our goal is to contribute to the advancement of more sophisticated and intelligent medical methods., Competing Interests: Conflict of Interest Statement. The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work., (© 2024. Huazhong University of Science and Technology.)

The evolution of insect metamorphosis has profoundly influenced their successful adaptation and diversification. Two key physiological processes during insect metamorphosis are notable: wing maturation and prothoracic gland (PG) histolysis. The ecdysone-induced protein 93 (E93) is a transcription factor indispensable for metamorphosis. While it has been established that both wing maturation and PG histolysis are dependent on E93, the molecular mechanisms through which E93 regulates these seemingly 'opposing' events remain poorly understood. In this study, time-course transcriptome profiles were generated for wing pads and PGs during metamorphosis in Blattella germanica, a hemimetabolous model insect. Comparative transcriptomic analyses demonstrated that E93 exerts predominant control over extensive gene transcription during wing morphogenesis and PG histolysis. During wing morphogenesis, E93 selectively enhances the expression of genes associated with cell proliferation, energy supply, signal transduction, actin cytoskeleton organization, and cell adhesion, etc. Additionally, E93 activates the transcription of the majority of genes within the wing gene network that are crucial for wing development in B. germanica. During PG histolysis, E93 preferentially promotes the expression of genes related to endocytosis, focal adhesion, the AMPK signaling pathway, adipocytokine signaling pathway, Toll and Imd signaling pathways, and autophagy, etc. The key genes involved in the aforementioned pathways were subsequently confirmed to contribute to the E93-dependent degeneration of the PG in B. germanica. In summary, our results reveal that E93 functions as a master transcriptional regulator orchestrating both tissue morphogenesis and histolysis during insect metamorphosis. These findings contribute to a deeper understanding of the genetic underpinnings of insect metamorphosis., Competing Interests: Declaration of Competing Interest The authors declare no competing or financial interests., (Copyright © 2024. Published by Elsevier Ltd.)

Aim: Physician visual assessment (PVA) in invasive coronary angiography (ICA) is clinically used to determine stenosis severity and guide coronary intervention. However, PVA provides limited information regarding the haemodynamic significance of stenosis. This prospective study aimed to develop a model combining visual diameter stenosis (DS PVA ) and quantitative coronary angiography (QCA)-derived parameters to diagnose ischaemic lesions using invasive fractional flow reserve (FFR) with pharmacologically induced maximal hyperaemia as the gold standard., Methods: A total of 103 patients (148 lesions) who underwent ICA and FFR measurement were included in the study. Quantitative coronary angiography was used to evaluate various parameters, including anatomical parameters such as lesion length (LL), minimal lumen diameter (MLD), and minimal lumen area, along with haemodynamic parameters like LL/MLD 4 and stenotic flow reserve (SFR). Plaque area, a characteristic parameter of plaque, was also assessed. Lesion-specific ischaemia was defined as invasive FFR ≤0.8., Results: The LL/MLD 4 (r= -0.66, p<0.001) and SFR (r=0.66, p<0.001) exhibited inverse and positive correlations, respectively, with invasive FFR. In the multivariable logistic regression analysis, LL/MLD 4 (≥10.6 mm -3 vs <10.6 mm -3 ; Odds ratio [OR] 10.59, 95% confidence interval [CI] 3.94-28.50; p<0.001) and SFR (≤2.85 vs >2.85; OR 4.38, 95% CI 1.63-11.79; p=0.004) were identified as the optimal dichotomised predictors for discriminating ischaemia. The area under the curve (AUC) was 0.77 using DS PVA ≥70% as a single predictor. Adding LL/MLD 4 ≥10.6 mm -3 and SFR ≤2.85 into the model significantly increased the AUC to 0.87 (p<0.001)., Conclusion: Incorporating QCA-derived haemodynamic parameters provided significant incremental value in the model's discriminatory capability for ischaemic lesions compared with visual diameter assessment alone., Competing Interests: Declaration of Competing Interest K.K.Y. has received research funding from Amgen, Astra Zeneca, Abbott Vascular, Bayer, Boston Scientific, Shockwave Medical, Novartis (via institution); Consulting fees from Abbott Vascular, Medtronic, Novartis, Peijia Medical; Speaker fees from Shockwave Medical, Abbott Vascular, Boston Scientific, Medtronic, Alvimedica, Biotronik, Orbus Neich, Shockwave Medical, Amgen, Novartis, Astra Zeneca, Microport, Terumo, Omnicare. K.K.Y. is also co-founder and owns equity in Trisail for which Orbus Neich is an investor., (Copyright © 2024 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate the efficacy of transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) for both primary and recurrent early-stage hepatocellular carcinoma (HCC) and to analyze the significant prognostic factors., Patients and Methods: Data from patients with early-stage primary or recurrent HCC who underwent TACE plus RFA between August 2019 and May 2024 were collected from three major general hospitals. 158 patients were divided into a primary group and a recurrent group on the basis of their baseline characteristics. Compared the objective response rate (ORR), 1-, 3-, and 5-year progression-free survival (PFS) rates, 1-, 3-, and 5-year overall survival (OS) rates, and complication rate between the two groups. Multivariate analyses were used to evaluate the factors influencing PFS and OS., Results: One hundred fifty-eight patients were enrolled. The ORRs of the primary and recurrent groups were 98.2% and 95.1%, respectively, with no statistically significant difference (χ 2 = 2.032, Ρ = 0.362). The primary group having a significantly longer PFS time than the recurrent group ( Ρ < 0.001). However, there was no significant difference in the 1-, 3-, and 5-year OS rates between the two groups ( Ρ = 0.218). Multivariate analysis revealed that primary or recurrent HCC and the Child‒Pugh score were significant prognostic factors for PFS, whereas the serum albumin level was a significant prognostic factor for OS., Conclusion: TACE plus RFA has similar clinical efficacy and safety for both primary and recurrent early HCC. Compared with patients with primary HCC, those with recurrent disease had significantly shorter PFS times., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Chen et al.)

In humans and nonhuman primates, the central 1° of vision is processed by the foveola, a retinal structure that comprises a high density of photoreceptors and is crucial for primate-specific high-acuity vision, color vision and gaze-directed visual attention. Here, we developed high-spatial-resolution ultrahigh-field 7T functional magnetic resonance imaging methods for functional mapping of the foveolar visual cortex in awake monkeys. In the ventral pathway (visual areas V1-V4 and the posterior inferior temporal cortex), viewing of a small foveolar spot elicits a ring of multiple (eight) foveolar representations per hemisphere. This ring surrounds an area called the 'foveolar core', which is populated by millimeter-scale functional domains sensitive to fine stimuli and high spatial frequencies, consistent with foveolar visual acuity, color and achromatic information and motion. Thus, this elaborate rerepresentation of central vision coupled with a previously unknown foveolar core area signifies a cortical specialization for primate foveation behaviors., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

A direct electrochemical sulfonylation between indoles, inorganic sulfites, and alcohols was developed, in which various indoyl sulfonate esters were prepared efficiently. In this transformation, the easy-handle and cost-effective inorganic sulfite was disclosed to engage in a Csp 2 -H sulfonylation as the SO 2 source in an undivided electrolysis cell under mild conditions. In addition, the unexpected paired electrosynthesis has been achieved, owing to the dual role of inorganic sulfites, and led to a sulfonylation/reduction sequence to rapidly deliver hydroxyl substituted indole sulfonate esters.

The pervasive presence of organophosphate pesticides (OPs), such as chlorpyrifos (CPF), in aquatic ecosystems underscores the urgent need for sensitive and reliable detection methods to safeguard environmental and public health. This study addressed the critical need for a novel biosensor capable of detecting CPF and its toxic metabolite, 3,5,6-trichloro-2-pyridinol (TCP), with high sensitivity and selectivity, suitable for field applications in environmental monitoring. The study engineered a whole-cell biosensor based on E. coli strains that utilize the ChpR transcriptional regulator and the vioABCE gene cluster, providing a distinct visual and colorimetric response to CPF and TCP. The biosensor's performance was optimized and evaluated across various water matrices, including freshwater, seawater, and soil leachate. The biosensor demonstrated high sensitivity with a broad linear detection range, achieving limits of detection (LODs) at 0.8 μM for CPF and 7.813 nM for TCP. The linear regression concentration ranges were 1.6-12.5 μM for CPF and 15.6-125 nM for TCP, aligning with environmental standard limits and ensuring the biosensor's effectiveness in real-world scenarios. This innovative biosensing approach offers a robust, user-friendly tool for on-site environmental monitoring, significantly mitigating OPs contamination and advancing current detection technologies to meet environmental protection standards., 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.)

The environmental risk of Cd in soils strongly depends on the mobilization of Cd in soils. However, limited knowledge exists on the redistribution of exogenic Cd inputs in soils, especially across diverse lithological regions. Herein, we aimed to investigate the fate of Cd in soils from two mining areas with contrasting lithologies (siliceous and calcareous) using stable Cd isotopes. The isotope tracing results confirm that mining activities are the main Cd source in both areas. The positive correlation between δ 114/110 Cd values and goethite/dolomite content indicates the release of heavy Cd isotopes during the dissolution of exogenetic minerals. Additionally, high contents of exchangeable Cd (11 % to 36 %) and Fe oxide-bound Cd (29 % to 42 %) drive plant pumps to transport heavy Cd isotopes from the deeper to upper horizons of the soils from the siliceous area. In the calcareous area, the total organic carbon content is positively correlated with the Cd concentration and δ 114/110 Cd value, suggesting potential complexation of Cd with organic matter due to the stabilizing effect of carbonate minerals on soil organic matter. This study highlights the different redistributions of exogenous Cd in soils from diverse lithological regions, emphasizing the need to consider regional lithology when developing soil quality standards for Cd., 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.)

The two-dimensional (2D) monolayer material MoSi 2 N 4 was successfully synthesized in 2020[Hong et al., Science 369, 670, (2020)], exhibiting a plethora of new phenomena and unusual properties, with good stability at room temperature. However, MA 2 Z 4 family monolayer materials involve primarily transition metal substitutions for M atoms. In order to address the research gap on lanthanide and actinide MA 2 Z 4 materials, this work conducts electronic structure calculations on novel 2D MSi 2 N 4 (M = La, Eu) monolayer materials by employing first-principles methods and CASTEP. High carrier mobility is discovered in the indirect bandgap semiconductor 2D LaSi 2 N 4 monolayer (~5400 cm 2  V -1  s -1 ) and in the spin (spin-down channel) carrier mobility of the half-metallic ferromagnetic EuSi 2 N 4 monolayer (~2800 cm 2  V -1  s -1 ). EuSi 2 N 4 monolayer supplements research on spin carrier mobility in half-metallic ferromagnetic monolayer materials at room temperature and possesses a magnetic moment of 5 μ B , which should not be underestimated. Furthermore, due to the unique electronic band structure of EuSi 2 N 4 monolayer (with the spin-up channel exhibiting metallic properties and the spin-down channel exhibiting semiconductor properties), it demonstrates a 100% spin polarization rate, presenting significant potential applications in fields such as magnetic storage, magnetic sensing, and spintronics., (© 2024 Wiley Periodicals LLC.)

The double spike (DS) technique is a highly effective approach for measuring the isotope ratios of many elements. However, it is common for some fraction of the prepared samples to be "overspiked." The usual solution for this problem involves repurifying and reanalyzing the samples to ensure data accuracy. Here, we propose a straightforward mathematical scheme to rectify the isotope ratios of overspiked samples, avoiding repetitive, time-consuming operations. The principle behind this scheme is that adding a standard solution with the certified isotope ratio decreases the overspiked ratio to the normal range. The related theoretical equations and a thorough error propagation model are presented. Taking nickel (Ni) isotopes as an example, we demonstrate how to utilize the spike-to-sample ratios of the overspiked sample and the sample-standard mixture, as well as the spike-subtracted isotope ratios of the mixture (δ 60 Ni mix ), to accurately determine the actual sample isotopes. This method's accuracy and precision (2SD) were evaluated by testing Ni, chromium (Cr), and cadmium (Cd) isotope measurements. Precision consistent with traditional DS measurements can be achieved when the fraction of the added standard solution (f std ) is ≤0.60 (60%) in the mixture or when the overspiked multiple is ≤2.5. The added standard solution is recommended to be the same as the standard used to define the delta scale (e.g., δ 60 Ni = 0.000‰) to simplify the calculation procedures. This method expands the application of DS from the normal to the overspiked range and can be extended to isotope analyses of many elements where DS is applicable.

Bismuth oxychalcogenides (Bi 2 O 2 X, X = S, Se, Te), a family of non-van der Waals (non-vdW) two-dimensional (2D) semiconductors, are attracting significant attention due to their outstanding semiconducting properties and huge potential in various applications of electronic and optoelectronic devices. Surface imperfections ( e.g. , surface vacancies) and surface reconstructions are more likely to appear and may cause intriguing physical properties and novel phenomena in the non-vdW 2D materials than the vdW cases. Here, we explore the impacts of surface vacancies and surface reconstructions on the properties of the surfaces and 2D structures of Bi 2 O 2 X by using the first-principles method. We find that the dimerization of surface X-vacancies occurs in Bi 2 O 2 S and Bi 2 O 2 Te (001) surfaces, like that happening in Bi 2 O 2 Se. Unexpectedly, the electronic structures of Bi 2 O 2 X (001) surfaces show strong tolerance to the order of surface X-vacancies. Furthermore, we find a phenomenon of thickness-dependent surface reconstructions for non-vdW Bi 2 O 2 X ultrathin films. For a monolayer, the zipper-surface is more stable, while the dimer-surface is generally more stable for thicker films. Calculated exfoliation energies of the Bi 2 O 2 X monolayer and multi-layers are close to those of common vdW 2D materials, indicating that 2D Bi 2 O 2 X belong to easily fabricated 2D materials, even though the inter-layer binding interaction is of the non-vdW type. Our results suggest that non-vdW 2D materials can possess intriguing properties because of surface imperfections and reconstructions in comparison with vdW 2D materials.

Aqueous Zn-ion batteries have garnered significant attention as promising and safe energy storage systems. Due to the inevitable dendrite and corrosion in metallic Zn anodes, alternative anodes of intercalation-type materials are desirable, but they still suffer from low energy efficiency, unsatisfactory capacity, and insufficient cycle life. Here, we develop a high-performance anode for aqueous Zn-ion batteries via a lattice expansion strategy in combination with a Zn 2+ /H + synergistic mechanism. The anatase TiO 2 with expanded lattice exhibits an appropriate deintercalation potential of 0.18 V vs Zn/Zn 2+ and a high reversible capacity (227 mAh g -1 at 2.04 A g -1 ) with an outstanding rate capability and excellent cycle stability. The high electrochemical performance is attributed to a decrease in the Zn 2+ /H + diffusion barriers, which results from lattice expansion and also a H + -promoted Zn 2+ intercalation effect. The anode intercalates Zn 2+ /H + via a solid-solution mechanism with a minor volume change, which contributes to the high reversibility and thus high energy efficiency. When paired with different types of cathodes, including NV, I 2 , and activated carbon, to construct corresponding full cells, high specific energy, high specific power, long cycle life, and extremely high energy efficiency can be achieved. This study provides a prospect for developing high-performance Zn-ion batteries.

Loss of phosphatase and tensin homolog (PTEN) has been linked to an immunosuppressive tumor microenvironment, but its underlying mechanisms remain largely enigmatic. Here, we report that PTEN can be secreted by the transmembrane emp24 domain-containing protein 10 (TMED10)-channeled protein secretion pathway. Inhibiting PTEN secretion from tumor cells contributes to immunosuppression and impairs the tumor-suppressive role of PTEN, while intratumoral injection of PTEN protein promotes antitumor immunity and suppresses tumor growth in mice. Mechanistically, extracellular PTEN binds to the plexin domain-containing protein 2 (PLXDC2) on macrophages, triggering subsequent activation of JAK2-STAT1 signaling, which switches tumor-associated macrophages (TAMs) from the immunosuppressive to inflammatory phenotype, leading to enhanced activation of CD8 + T and natural killer cells. Importantly, PTEN treatment also enhances the therapeutic efficacy of anti-PD-1 treatment in mice and reverses the immune-suppressive phenotype of patient-derived primary TAMs. These data identify a cytokine-like role of PTEN in immune activation and tumor suppression and demonstrate the therapeutic potential for extracellular administration of PTEN in cancer immunotherapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Older age is associated with greater likelihood of urinary incontinence and unmet care needs. It was hypothesized that age might influence clinical and ultrasound outcomes of transobturator mid-urethral sling (TOS) surgery. The aim of this study was to compare 1-year postoperative clinical and ultrasonographic outcomes of TOS surgery among women of different ages., Methods: A retrospective analysis of a cohort of women who underwent primary and isolated TOS surgery for uncomplicated urodynamic stress incontinence was undertaken. All women underwent pre-operative and 1-year postoperative evaluations including clinical interview, pelvic examination, urodynamic studies and introital four-dimensional ultrasound. To be eligible for surgery, women needed to be independent in their daily life, and to have an acceptable level of surgical risk on pre-operative assessment. The primary outcome was the rate of stress urinary incontinence (SUI) after surgery. The secondary outcomes comprised postoperative adverse events and ultrasound findings., Results: In total, 162, 213, 60 and 29 women aged <51, 51-64, 65-74 and ≥75 years, respectively, were included in this study. At 1-year postoperative assessment, older women were more likely to report SUI and bothersome SUI, while the severity of SUI and postoperative adverse events were similar in older women compared with other age groups. Ultrasound revealed that the sling tended to be looser and higher in older women., Conclusion: TOS surgery is effective and safe for women of all ages who are independent in their daily life and who have an acceptable level of surgical risk. The sling tended to be looser and higher in older women., 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.)

Ginseng, with various pharmacological activities, has received increasing attention to improve cardiovascular health (CVH). Therefore, this meta-analysis synthesized the effect of ginseng consumption on biomarkers of CVH in adults. A systematic search was performed in the databases of PubMed, Scopus, Web of Science, Embase, and the Cochrane Library through July 24, 2023 to screen out English-language randomized controlled trials (RCTs) evaluating the effects of ginseng consumption on body composition, blood pressure, vascular stiffness, lipid metabolism, glucose metabolism, insulin resistance, inflammatory cytokines, and adipocytokines in adults. The weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate the overall effect size, and STATA 12.0 was used for comprehensive analysis. Forty-five studies were included in the meta-analysis. Ginseng consumption significantly reduced systolic blood pressure (SBP) (WMD = -2.57 mmHg, 95% CI = -4.99 to -0.14, p = 0.038), total cholesterol (TC) (WMD = -4.40 mg/dL, 95% CI = -8.67 to -0.132, p = 0.043), low density lipoprotein cholesterol (LDL-C) (WMD = -2.81 mg/dL, 95% CI = -4.89 to -0.72, p = 0.008), C-reactive protein (CRP) (WMD = -0.41 mg/L, 95% CI = -0.73 to -0.10, p = 0.010), and interleukin-6 (IL-6) (WMD = -2.82 pg./mL, 95% CI = -4.31 to -1.32, p < 0.001). Subgroup analyses suggested that supplementation with ginseng for less than 12 weeks significantly reduced SBP, but 12 weeks or more improved TC and CRP. Ginseng consumption on SBP, TC, and CRP seemed to be more effective on unhealthy participants. The meta-analysis showed that ginseng consumption might have the potential to improve SBP, TC, LDL-C, CRP, and IL-6. These findings suggest that ginseng is a potential candidate for the maintenance of CVH. However, our results had high heterogeneity. Future high-quality studies are needed to firmly establish the clinical efficacy of ginseng consumption., (© 2024 John Wiley & Sons Ltd.)

The increasing use of silica nanoparticles (SiO 2 NPs) has raised concerns about potential human exposure. Assessing the health risks associated with SiO 2 NPs necessitates understanding their cellular uptake, yet measuring this uptake at low, environmentally relevant concentrations presents a significant challenge. In this study, we synthesized core-shell structured Au@SiO 2 NPs with diameters ranging from 50 to 200 nm and quantified their cellular uptake by analyzing the concentrations of Si and Au in A549 human lung carcinoma cells. No significant differences in cytotoxicity or cellular uptake were observed between Au@SiO 2 NPs and their core-less counterparts. Additionally, the comparable cellular uptake of Au@SiO 2 NPs, as evidenced by both Si and Au content, supports the use of the Au core as a tracer for SiO 2 NP uptake. The inclusion of the Au core facilitated the examination of SiO 2 NP uptake at concentrations an order of magnitude lower than previously possible, aligning more closely with environmental exposure levels. This is important because uptake at low concentrations cannot be accurately predicted from high-concentration data due to concentration-dependent changes in particle aggregation. Overall, Au@SiO 2 NPs provide a precise method for evaluating SiO 2 NP uptake at low concentrations, offering a more realistic assessment of their potential health risks compared to studies conducted at higher concentrations., 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.)

Carrot (Daucus carota L.), a widely cultivated economically vegetable from the Apiaceae family, is grown globally. However, carrots can be adversely impacted by cadmium (Cd) pollution in the soil due to its propensity to accumulate in the fleshy root, thus impeding carrot growth and posing health hazards to consumers. Given the potential of hydrogen sulfide (H 2 S) to improve plant resistance against Cd stress, we treated germinating carrot seeds with varying concentrations of sodium hydrosulfide (NaHS), aiming to alleviate the toxic impacts of Cd stress on carrot seed germination. The results revealed that carrot seeds treated with a concentration of 0.25 mM NaHS displayed better seed germination-associated characteristics compared to seeds treated with NaHS concentrations of 0.1 mM and 0.5 mM. Further investigation revealed a rise in the expression levels of L-cysteine desulfhydrase and D-cysteine desulfhydrase, along with enhanced activity of L-cysteine desulfhydrase and D-cysteine desulfhydrase among the NaHS treatment group, thereby leading to H 2 S accumulation. Moreover, NaHS treatment triggered the expression of pyrroline-5-carboxylate synthase and pyrroline-5-carboxylate reductase and promoted the accumulation of endogenous proline, while the contents of soluble sugar and soluble protein increased correspondingly. Interestingly, since the application of exogenous proline did not influence the accumulation of endogenous H 2 S, suggesting that H 2 S served as the upstream regulator of proline. Histochemical staining and biochemical indices revealed that NaHS treatment led to elevated antioxidant enzyme activity, alongside a suppression of superoxide anion and hydrogen peroxide generation. Furthermore, high performance liquid chromatography analysis revealed that NaHS treatment reduced Cd 2+ uptake, thereby promoting germination rate, seed vitality, and hypocotyl length of carrot seeds under Cd stress. Overall, our findings shed light on the application of NaHS to enhance carrot resistance against Cd stress and lay a foundation for exploring the regulatory role of H 2 S in plants responding 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 © 2024 Elsevier GmbH. All rights reserved.)

The biological function against obesity of heat shock protein Hsp72 in adipose tissue has remained unclear. Our findings demonstrated that the expression levels of Hsp72 increased during the triglyceride (TG) accumulation process both in adipose tissue and 3T3-L1 cells. A significant decrease in adipogenic gene expression and TG levels was observed upon Hsp72 knockdown in 3T3-L1 cells, suggesting that Hsp72 promoted adipogenic differentiation and lipid synthesis processes. Encouraged by these findings, we further confirmed the allosteric Hsp72 inhibitors YK5 and MKT-077 also exhibited inhibition of both these processes. Further evaluation revealed that Hsp72 played a key role in interacting with numerous novel metabolic and cytomorphologic-related client proteins, thereby mediating the adipogenesis and lipogenesis process. Hsp72 inhibitors had the potential to disrupt these interactions, leading to the downregulation of adipogenic and lipogenic gene expression, as well as the suppression of TG accumulation. These findings suggested that inhibiting Hsp72 to disrupt adipogenic differentiation and lipid synthesis in adipocytes may be a promising anti-obesity strategy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Fibrosis is a process involving excessive accumulation of extracellular matrix components, the severity of which interferes with the function of the organ in question. With the advances in RNA sequencing and in-depth molecular studies, a large number of current studies have pointed out the irreplaceable role of non-coding RNAs (ncRNAs) in the pathophysiological development of organ fibrosis. Here, by summarizing the results of a large number of studies on the interactions between ncRNAs, some studies have found that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), among others, are able to act as sponges or decoy decoys for microRNAs (miRNAs), act as competing endogenous RNAs (ceRNAs) to regulate the expression of miRNAs, and subsequently act on different mRNA targets, playing a role in the development of fibrosis in a wide variety of organs, including the heart, liver, kidneys, and spleen. parenchymal organs, including heart, liver, kidney, and spleen, play important roles in the development of fibrosis. These findings elucidate the intricate involvement of the lncRNA/circRNA-miRNA-mRNA axis in the pathophysiological processes underpinning organ fibrosis, thereby enhancing our comprehension of the onset and progression of this condition. Furthermore, they introduce novel potential therapeutic targets within the realm of ncRNA-based therapeutics, offering avenues for the development of innovative drugs aimed at mitigating or reversing the effects of organ fibrosis., 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. None, (Copyright © 2024. Published by Elsevier Inc.)

Background: The robotic hair transplant technology, ARTAS, has a series of fine mechanical structure and an intelligent recognition system that allows it to independently select hair follicular units (FUs) and effectively harvest hair. After entering China in 2016, ARTAS has attracted the attention of hair transplant surgeons and hair loss patients given its advantages in a short learning curve and simple operation., Objective: To compare the efficacy and safety between the ARTAS system and follicular unit excision (FUE) in the treatment of male androgenetic alopecia (AGA) and to further promote the improvement and upgrading of ARTAS technology concerning hair transplantation., Methods: Thirteen Chinese male patients with Norwood-Hamilton II-IV AGA aged 25-35 years were enrolled in this study. The donor site of each patient was randomly divided into left and right regions, receiving ARTAS on one side and FUE on the other. Yield, transection, and discard rates of hair FUs from both sides were compared. Safety of the procedures in whole, as well as follow-up results were investigated and evaluated., Results: The total yield rate on the ARTAS side was lower than on the FUE side (82.05% vs. 90.03%, p > 0.05); the total discard rate on the ARTAS side was higher than on the FUE side (10.71% vs. 5.46%, p < 0.05); the total transection rate on the ARTAS side was lower than on the FUE side (13.17% vs. 13.96%, p > 0.05). No significant difference was found in patient satisfaction (efficacy), and no side effects or complications were detected during or after all surgeries., Conclusion: The current iteration of Robotic hair transplant technology is effective and safe, and can be recommended for AGA hair transplantation surgery., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Introduction: Colorectal cancer (CRC) represents a significant health burden worldwide, with a notable increase in early-onset colorectal cancer (EOCRC) cases, defined as those diagnosed before the age of 50 years., Materials and Methods: Using data from Taiwan's national cancer registry and a retrospective cohort from Chang Gung Memorial Hospital, this study analyzed CRC cases diagnosed between 2008 and 2019. The analysis compared the EOCRC and late-onset CRC (LOCRC) groups in terms of clinicopathological characteristics, pre-diagnostic symptoms, and survival outcomes., Results: The analysis revealed a continuous increase in the annual incidence of EOCRC, with colon cancer and rectal cancer rising by 3.2 % and 3.3 %, respectively. Patients with EOCRC presented with more aggressive disease characteristics, such as signet-ring cell adenocarcinoma, mucinous adenocarcinoma, and poorly differentiated grade. Advanced stages at diagnosis, stages III and IV, were more common with EOCRC (62.4 %) than with LOCRC (50.3 %). Patients with EOCRC reported rectal bleeding, changes in bowel habits, and abdominal pain more frequently than those in the LOCRC group. There is a strong association between stool-related symptoms and left-sided CRC. Despite similar surgical outcomes, the 5-year cancer-specific survival rate of patients with stage IV EOCRC was significantly lower than that of patients with LOCRC (32.8 % vs. 51.9 %, p = 0.012)., Conclusion: This study highlights a persistent rise in the incidence of EOCRC, with patients presenting with more aggressive disease and experiencing inferior survival. These findings underscore the importance of heightened awareness and early detection strategies for CRC, especially in younger populations, to improve the prognosis., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The optimal prehospital blood pressure in patients following traumatic brain injury (TBI) remains controversial. We aimed to assess the association between the systolic blood pressure (SBP) at emergency department triage and patient outcomes following isolated moderate-to-severe TBI. We conducted a cross-national multicenter retrospective cohort study using the Pan-Asia Trauma Outcomes Study database from January 1, 2016, to November 30, 2018. The enrollees were adult patients with isolated moderate-to-severe TBI defined by the International Classification of Diseases code, a Glasgow Coma Scale (GCS) <13 at triage, and a nonhead Abbreviated Injury Scale ≤3. The studied variables were SBPs at triage categorized into different ranges. The primary outcome was 30-day mortality, and the secondary outcome was poor functional status at hospital discharge defined by the modified Rankin Scale ≥4. Multivariable logistic regression was applied to adjust for confounders including country, sex, age, mechanism of injury, prehospital vascular access, respiratory rate, GCS, oxygen saturation, intubation, Injury Severity Score, head surgery, intensive care unit admission, and length of hospital stay. Subgroup analyses were performed on different severity of TBI. A total of 785 patients (median age, 42 years; male patients 77.5%; mean SBP at triage, 136.3 ± 33.1 mmHg) were included in the primary analysis. The lowest 30-day mortality rate existed in patients with SBP of 100-119 mmHg. Taking it as baseline, the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of SBP <100 mmHg, 120-139 mmHg, 140-159 mmHg, and ≥160 mmHg were 7.05 (2.51-19.78), 3.14 (1.14-8.65), 2.91 (1.04-8.17), and 3.28 (1.14-9.42). As for the secondary outcome, the aORs and 95% CIs were 1.36 (0.68-2.68) of <100 mmHg, 0.99 (0.57-1.70) of 120-139 mmHg, 1.23 (0.67-2.25) of 140-159 mmHg, and 1.52 (0.78-2.95) of ≥160 mmHg. Subgroup analyses revealed trends of the best outcomes in both moderate and severe TBI patients with SBP 100-119 mmHg, whereas statistical significance appeared only in patients with severe TBI. SBP of 110-119 mmHg at triage is associated with the lowest 30-day mortality in patients following isolated moderate-to-severe TBI and possibly related to a better functional outcome.

The tanning hormone, Bursicon, is a neuropeptide secreted by the insect nervous system that functions as a heterodimer composed of Burs-α and Burs-β subunits. It plays a critical role in the processes of cuticle tanning and wing expansion in insects. In this study, we successfully identified the AcBurs-α and AcBurs-β genes in Aphis citricidus. The open reading frames of AcBurs-α and AcBurs-β were 480 and 417 bp in length, respectively. Both AcBurs-α and AcBurs-β exhibited 11 conserved cysteine residues. AcBurs-α and AcBurs-β were expressed during all developmental stages of A. citricidus and showed high expression levels in the winged aphids. To investigate the potential role of AcBurs-α and AcBurs-β in wing development, we employed RNA interference (RNAi) techniques. With the efficient silencing of AcBurs-α (44.90%) and AcBurs-β (52.31%), malformed wings were induced in aphids. The proportions of malformed wings were 22.50%, 25.84%, and 38.34% in dsAcBurs-α-, dsAcBur-β-, and dsAcBurs-α + dsAcBur-β-treated groups, respectively. Moreover, feeding protein kinase A inhibitors (H-89) also increased the proportion of malformed wings to 30.00%. Feeding both double-stranded RNA and inhibitors (H-89) significantly downregulated the wing development-related genes nubbin, vestigial, notch and spalt major. Silence of vestigial through RNAi also led to malformed wings. Meanwhile, the exogenous application of 3 hormones that influence wing development did not affect the expression level of AcBursicon genes. These findings indicate that AcBursicon genes plays a crucial role in wing development in A. citricidus; therefore, it represents a potential molecular target for the control of this pest through RNAi-based approaches., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

The flavonoid compound chinonin is one of the main active components of Rhizoma anemarrhena with multiple activities, including anti-inflammatory and antioxidant properties, protection of mitochondrial function and regulation of immunity. In this paper, we reviewed recent research progress on the protective effect of chinonin on brain injury in neurological diseases. "Chinonin" OR "Mangiferin" AND "Nervous system diseases" OR "Neuroprotection" was used as the terms for search in PumMed. After discarding duplicated and irrelevant articles, a total of 23 articles relevant to chinonin published between 2012 and 2023 were identified in our study.

Introduction: Chronic kidney disease is related to neurodegeneration and structural changes in the brain which might lead to cognitive decline. The Fazekas scale used for assessing white matter hyperintensities (WMHs) was associated with poor cognitive performance. Therefore, this study investigated the associations between the mini-mental status examination (MMSE), Montreal cognitive assessment (MoCA), cognitive abilities screening instrument (CASI), and Fazekas scale in patients under hemodialysis (HD)., Methods: The periventricular (PV) WMHs and deep WMHs (DWMHs) in brain magnetic resonance images of 59 patients under dialysis were graded using the Fazekas scale. Three cognition function tests were also performed, then multivariable ordinal regression and logistic regression were used to identify the associations between cognitive performance and the Fazekas scale., Results: There were inverse associations between the three cognitive function tests across the Fazekas scale of PVWMHs ( p  = .037, .006, and .008 for MMSE, MoCA, and CASI, respectively), but the associations were attenuated in the DWMHs group. In CASI, significant differences were identified in short-term memory, mental manipulation, abstract thinking, language, spatial construction, and name fluency in the PVWMHs group. However, DWMHs were only significantly correlated with abstract thinking and short-term memory., Conclusion: An inverse correlation existed between the Fazekas scale, predominantly in PVWMHs, and cognition in patients undergoing HD. The PVWMHs were associated with cognitive performance assessed by MMSE, MoCA, and CASI, as well as with subdomains of CASI such as memory, language and name fluency in patients undergoing HD.

Objective: To analyze the current treatment status and prognostic regression of the chronic NK cell lymphoproliferative disorder (CLPD-NK)., Methods: We retrospectively analyzed the clinical features, treatment and prognosis of 18 patients with CLPD-NK who were treated at our Hospital between September 2016 and September 2022., Results: Eighteen patients were included: three patients were treated with chemotherapy, five patients underwent immune-related therapy, one patient was treated with glucocorticoids alone, five patients were administered granulocyte colony-stimulating factor, blood transfusion therapy, or anti-infection therapy, followed by observation and follow-up, and four patients were observed without treatment. Fifteen patients survived, including two patients who achieved complete remission (CR) and seven patients who achieved partial remission (PR), of whom one patient progressed to Aggressive NK-cell leukemia (ANKL) and sustained remission after multiple lines of treatment; three patients were not reviewed, of which one patient was still in active disease, three patients developed hemophagocytic syndrome during treatment and eventually died, one of them had positive Epstein-Barr virus (EBV) expression. The 5-years overall survival rate was 83%., Conclusion: Most patients with CLPD-NK have inert progression and a good prognosis, whereas some patients have a poor prognosis after progressing to ANKL and combined with hemophagocytic syndrome. Abnormal NK cells invading the center suggest a high possibility of ANKL development, and immunosuppressants and hormones are effective treatments for this disease.

Acute postoperative urinary retention (APOUR) is 1 of the most common complications of spinal surgery, impacting both postoperative care and the patients' quality of life. This study is designed to investigate the risk factors and the incidence of APOUR after spinal surgery in Taiwan. We conducted a retrospective analysis using the Taiwanese National Health Insurance Research Database (NHIRD), a nationwide cohort of patients who underwent spinal surgery from the year 2000 to 2013. Patients suffering from APOUR were collected and perioperative parameters were recorded. The risk factors related to APOUR after spinal surgery were examined using multivariate logistic regression analysis. A total of 16,160 patients who underwent spinal surgery were retrieved from NHIRD. Among them, 432 (2.67%) suffered from acute urinary retention after surgery. Multivariate logistic regression analysis revealed that age (adjusted odds ratio [OR] = 1.02, 95% CI = 1.01-1.02), male gender (adjusted OR = 1.35, 95% CI = 1.10-1.60) and undergoing spinal surgery more than 2 times (adjusted OR = 4.78, 95% CI = 2.49-9.20) were statistically significant risk factors for APOUR after spinal surgery. The results of this retrospective cohort study suggest that patients undergoing spinal surgery more than 2 times, male gender and advanced age are significantly associated with an increased risk of APOUR after spinal surgery. This information may assist surgeons to identify patients who have a high risk of APOUR after spinal surgery and proactively provide them with early intervention., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Tuberculosis is a serious, infectious, zoonotic disease caused by Mycobacterium tuberculosis. Infections are transmitted in humans and livestock via aerosols. Rv1048c is a hypothetical unknown protein in the standard strain of Mycobacterium tuberculosis H37Rv. Rv1048c exists only in pathogenic Mycobacterium tuberculosis and is highly conserved; however its function is still unclear. The recombinant Mycobacterium smegmatis strain Ms&#95;Rv1048c, with heterologous expression of the Rv1048c gene, was constructed by using the pMV261 expression plasmid. The biological characteristics of the recombinant bacteria were studied, such as their growth pattern, drug resistance, and virulence. Expression of Rv1048c significantly reduced the growth rate of the strain, enhanced its ability to form a biofilm, and reduced its tolerance to sodium dodecyl sulfate, H 2 O 2 , and various anti-tuberculosis drugs, and reduced the viability of infected RAW264.7 macrophages. Rv1048c also significantly reduced the level of early pro-inflammatory factors in infected RAW264.7 cells. Rv1048c protein is considered to be a virulence protein that might regulate the growth of M. tuberculosis strains. The results of the present study indicate that Rv1048c plays an important role in Mycobacterial infection., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone, or 6PPD-Q) has received increasing attention as an emerging hotspot contaminant. The occurrence of 6PPD-Q in dust and fine atmospheric particles indicates substantial human exposure to this toxicant but the hazards of 6PPD-Q to human health is unknown. We used in silico approaches to identify potential human protein targets of 6PPD-Q and conducted preliminary validation through an in vitro cell proliferation assay and an in vivo transcriptomic analysis of prostate tissues from 6PPD-Q-treated mice. Receptor-based reverse screening and network pharmacology identified four hub targets of 6PPD-Q that were closely related to prostate carcinogenesis. Among these four targets, 6PPD-Q exhibited a strong binding tendency to androgen receptor (AR) with a binding free energy of -23.04 kcal/mol. A support vector machine (SVM) model for predicting chemicals with AR agonism or AR-inactivity was established with good prediction performance (mean prediction accuracy: 0.92). SVM prediction and AR-mediated cell-based assays, with a known AR agonist and a proposed AR inactive agent as positive and negative controls, confirmed that 6PPD-Q displayed AR agonism. Upregulation of Ar mRNA expression (FC = 1.29, p = 0.0404) and its related prostate cancer pathway was observed in the prostate of mice exposed to environmentally realistic concentrations of 6PPD-Q, suggesting a potential role in promoting prostate carcinogenesis. These findings provide evidence that 6PPD-Q agonized AR to exert downstream gene transactivation and imply its prostate cancer risks to humans., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Seven new polyketide compounds, four naphthoquinone derivatives, neofusarubins A-D ( 1 , 3 , 5 , and 18 ) and three graminin-like compounds, fusofuranones A-C ( 19 - 21 ), together with 14 known naphthoquinone derivatives, were isolated from the solid fermentation of Fusarium solani , an endophytic fungus obtained from medicinal plant as tea, Camellia chrysantha . The structures of new compounds were elucidated based on chemical evidence and spectral data analysis (1D and 2D-NMR, HR-ESI-MS, ECD, SC-XRD). Among the isolated compounds tested, 2-acetonyl-3-methyl-5-hydroxy-7-methoxy-naphthazarin ( 11 ) exhibited the most potent inhibitory activity against pancreatic cancer in PANC-1, MiaPaCa-2, and BxPC-3 cells. Network pharmacology analysis revealed that compound 11 inhibited cell proliferation and promotion of apoptosis by targeting epidermal growth factor receptor (EGFR), which were confirmed by cellular thermal shift assay (CETSA), microscale thermophoresis (MST) and EGFR stably knockdown cells model assay, respectively. In addition, molecular mechanism studies in vitro showed that 11 could suppress the growth of pancreatic cancer cells by targeting EGFR and effectively inhibit downstream PI3K/Akt signaling pathway. Collectively, these findings provide a new EGFR targeting natural product for the treatment of pancreatic cancer.

Four undescribed cytochalasins (1-4), three undescribed orsellinic acid derivatives (5-7) and two known metabolites including methyl lecanorate (8) and methyl orsellinate (9) were isolated from the solid-state cultivation of a soil-derived fungus Trichocladium asperum SQ2-3 collected in Qinghai-Tibet Plateau. Their structures were elucidated by analysis of NMR (1D and 2D) and mass spectrometry data. The absolute configurations of 1-7 were assigned by a combination of the modified Mosher's method, microscale derivatization and Mo 2 (OAc) 4 -induced circular dichroism experiment. Compounds 1, 2, 3 and 6 showed significant cytotoxicity against HL-60, A3494, SMMC-7721, MDA-MB-231 and SW480 cell lines with IC 50 values ranging from 4.74 to 15.84 μM, respectively. Meanwhile, compound 1 could obviously damage mitochondrial membrane potential and induce G2/M cell cycle arrest in A549 cells., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rationale: The Bronchiectasis Health Questionnaire (BHQ) is a concise, self-administered and disease-specific instrument for measuring health-related quality-of-life (HRQoL) in bronchiectasis., Objectives: To investigate the psychometric properties of simplified Mandarin BHQ and determine the minimum clinically important difference (MCID) as a reliable clinical endpoint for assessing the efficacy of bronchiectasis treatments., Methods: A longitudinal, randomized controlled trial cohort of 357 patients treated with tobramycin inhalation solution or saline inhalation for Pseudomonas aeruginosa infection, along with a cross-sectional observational cohort including 436 patients with bronchiectasis were analyzed. Psychometric analyses encompassed convergent validity, known-groups validity, internal consistency, test-retest reliability, and responsiveness. Both anchor-based and distribution-based approaches were utilized to calculate the MCID for therapeutic response., Results: There were significant positive correlations between BHQ scores and the Quality of Life - Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS), with correlation coefficient 0.698 in the trial cohort and 0.567 in the clinical cohort (both P<0.0001). Known-groups validity indicated significant differences in BHQ scores stratified by baseline Bronchiectasis Severity Index. BHQ scores correlated modestly with both FEV1% predicted and exacerbation frequency within the previous year. In the trial cohort, BHQ demonstrated excellent internal consistency (Cronbach's alpha: 0.893) and test-retest reliability (intraclass correlation coefficient: 0.853). An 8-point improvement in QoL-B-RSS corresponded to a mean increase of 5.49 points in BHQ scores after 4-week treatment. The MCID for BHQ was consistently 3 points., Conclusions: The BHQ (MCID: 3 points) represents a clinically meaningful tool for evaluating therapeutic intervention outcomes and patient-centered outcomes in patients with bronchiectasis.

Objective: To investigate the clinical efficacy of posterior unilateral biportal endoscopic(UBE) cervical discectomy for cervical radiculopathy under general anesthesia., Methods: A retrospective analysis of 35 patients with cervical disc herniation uderwent posterior UBE cervical discectomy under general anesthesia from March 2021 to March 2023 was performed, including 17 males and 18 females, with an average age of (56.00±7.79) years old ranging from 42 to 69 years old. The non-operative treatment time was 6 to 27 weeks with an average of(16.03±4.56) weeks. MRI showed lateral cervical disc herniation in 19 cases and foraminal cervical disc herniation in 8 cases. The pathological segments distribution was as follows L 4,5 in 5 cases, C 5,6 in 12 cases C 6,7 in 18 cases. CT/MRI was performed 1 to 3 d after surgery to evaluate the decompression, and the visual analogue scale(VAS), the Japanese Orthopedic Association(JOA) score, the stability of cervical spine surgery segment and the change of intervertebral height were recorded., Results: All 35 patients successfully completed the operation, and the operation time was (55.88±5.02) min, the hospital stay after surgery (3.53±0.74) d. All 35 patients were followed up from 12 to 24 months with an average of (14.53±2.32) months. The VAS of preoperative, postoperative 1 day and 12 months were (7.000±0.875), (2.540±0.611), (2.143±0.772), respectively, the VAS at each time point before and after surgery were statistically significant( P <0.05). The JOA scores of preoperative, postoperative 1 day and 12 months were (11.660±0.533), (16.430±0.655), (16.540±0.611), respectively. The intervertebral height of the lesion segment at preoperative and 12 months was (6.206±0.493) mm and (6.147±0.497) mmm, respectively, and the difference was not statistically significant( P >0.05). None of the patients had cervical spine segment instability before or after surgery. According to the modified Macnab criteria, the clinical efficacy was evaluated at 12 months after operation, 32 cases were excellent, 2 cases were good, and 1 case was good., Conclusion: UBE cervical discectomy is a minimally invasive, safe and effective surgical method for the treatment of single-segment cervical disc herniation, which may be an alternative to the treatment of cervical foraminal herniation, but due to the small sample size and short follow-up time, its long-term efficacy needs to be further observed.

Sedum plumbizincicola (Sp) is a cadmium (Cd) hyperaccumulator found specifically in abandoned ancient mines where N is regularly deficient while Cd presents in excess. How Sp got adapted to this unique habitat remains unknown. Here, we reported relative abundant presence of NH 4 + in mine areas for Sp, and the isolation and functional characterisation of a putative NH 4 + transporter gene AMT1;2, which is highly expressed in Sp roots and encodes a pH-dependent dual affinity ammonium uptake transporter. Compared to SaAMT1;2, the homologous gene in the nonhyperaccumulating control Sedum alfredii (Sa), SpAMT1;2 expression is much higher and not inhibited by Cd. Only eight amino acid sequence polymorphisms were observed between SpAMT1;2 and SaAMT1;2, and the in-vitro NH 4 + uptake activity and subcellular localisation are identical between them with or without Cd stress. Moreover, in contrast in Sa, NH 4 + uptake in Sp is not inhibited by Cd, and NH 4 + at ambient level promotes Cd accumulation. These data suggest that SpAMT1;2 is likely an essential gene contributing to nitrogen nutrition and the interaction between NH 4 + and Cd uptake in Sp, which might represent a novel N utilisation pathway evolved in mines for the hyperaccumulator Sp., (© 2024 John Wiley & Sons Ltd.)

Background: A significant research gap exists regarding the role of tissue exosomes in intrauterine adhesions (IUAs). This study aims to investigate the involvement of miR-195-5p and its regulatory network in IUAs through the analysis of tissue exosomes., Methods: Exosomes from rat uterine tissue with intrauterine adhesions were analyzed via transcriptomics to identify downstream target genes of miR-195-5p, cross-referencing with the human endometrial transcriptomics database GSE224093. Dual luciferase labeling confirmed miRNA-target gene interactions. The therapeutic efficacy of a miR-195-5p agonist was assessed in vivo through HE staining, Masson staining, and mating tests. The mechanisms underlying extracellular matrix (ECM) deposition and myofibroblast transdifferentiation in endometrial fibrosis were investigated both in vitro and in vivo using RT-PCR, Western Blot, immunofluorescence, and immunohistochemistry. Migration ability of endometrial stromal cells was evaluated using CCK8, scratch tests, and Transwell assays. Finally, the clinical potential of miR-195-5p was compared with autologous adipose-derived mesenchymal stem cells., Results: The expression of miR-195-5p in uterine tissue exosomes from intrauterine adhesions was found to be decreased. Treatment with a miR-195-5p agonist resulted in improved endometrial health, reduced fibrosis, increased glandular density, and enhanced birth rates in rats. Both in vivo and in vitro experiments confirmed that miR-195-5p decreased ECM deposition, reduced myofibroblast transdifferentiation, and inhibited the migration of endometrial stromal cells. This was achieved through the downregulation of YAP expression in the Hippo pathway and the upregulation of Smad7. Notably, the therapeutic efficacy of miR-195-5p agonists was comparable to that of stem cell therapy, offering promising avenues for clinical application., Conclusions: Differential expression of miR-195-5p in tissue exosomes can reduce ECM deposition and myofibroblast transdifferentiation, improving endometrial fibrosis by regulating the YAP-Smad7 pathway in the Hippo signaling cascade., Competing Interests: Declarations. Ethics approval and consent to participate: This study involves the collection of human endometrium and animal as part of the project titled ‘Study on the mechanism of miR-195-5p improving the epithelial-mesenchymal transformation of endometrial adhesion through YAP-SMAD7, which was approved by the Second Affiliated Hospital of Fujian Medical University Animal Care Committee (Approval No. and Date: 2023-179, May 18, 2023). Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Lung cancer is the most common cause of cancer mortality globally, and the prevalence of lung adenocarcinoma (LUAD), the most common lung cancer subtype, has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in non-smokers. Here, we performed whole exome-sequencing and RNA-sequencing of samples from 94 East Asian patients with precancerous lesions (25 with atypical adenomatous hyperplasia [AAH]; 69 with adenocarcinoma in situ [AIS]) and 73 patients with early invasive lesions (minimally invasive adenocarcinoma [MIA]). Cellular analysis revealed that the activities of endothelial and stromal cells could be used to categorize tumors into molecular subtypes within pathologically defined types of lesions. The subtypes were linked with the radiologically defined type of lesions and corresponded to immune cell infiltration throughout the early progression of LUAD. Spatial transcriptomic analysis revealed the distribution of epithelial cells, endothelial cells, fibroblasts, and plasma cells within MIA samples. Characterization of the molecular lesion subtypes identified positively selected mutational patterns and suggested that angiogenesis in the late-stage AIS type potentially contributes to tissue invasion of the MIA type. This study offers a resource that may help to improve early diagnosis and patient prognosis, and the findings suggest possible approaches for early disease interception.

Perovskite light-emitting diodes (PeLEDs) are promising for next-generation high-definition displays. One of the keys to achieving high performance PeLEDs lies in how to fabricate crystalline and dense perovskite films. However, there exist challenges to directly grow well-crystallized CsPbBr 3 nanocrystal thin films on transport layers due to low solubility in solvents and fast precipitation of all-inorganic CsPbBr 3 , and the corresponding bright, efficient, and stable green PeLEDs have rarely been reported. Herein, we report an efficient strategy to prepare well-crystallized and dense CsPbBr 3 nanocubes for ultrabright and efficient green PeLEDs. We introduce sulfobetaine zwitterion as crystallization control agent and strontium fluoride nanocrystals as nucleation seeds to grow high-quality CsPbBr 3 nanocube films. Eventually, the CsPbBr 3 films enable green PeLEDs with a maximum luminance of 162 767 cd m -2 and a champion external quantum efficiency of 21.3% along with a narrow spectral line width of ∼14.7 nm, representing state-of-the-art performances in green PeLEDs.

Background: Knee osteoarthritis (KOA) is characterized by mitochondrial damage and increased inflammation. Circulating cell-free mitochondrial DNA (ccf-mtDNA), which originates from damaged mitochondria, is an endogenous damage-associated molecular pattern (DAMPs) molecule that may trigger inflammation and is recognized as a potential biomarker for various diseases. In this study, we investigated the potential association between plasma ccf-mtDNA content and its use as a diagnostic biomarker in patients with KOA., Methods: We collected plasma samples from patients with KOA and healthy controls (HC). Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect ccf-mtDNA content in the plasma samples. We used the Kellgren-Lawrence (K-L) classification criteria to classify patients with KOA into four grades: I-IV. Disease severity in patients with KOA was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Next, Spearman analysis was performed to observe the correlation between ccf-mtDNA content and the K-L classification and WOMAC score. Logistic regression analysis was used to evaluate the relationship between ccf-mtDNA and KOA risk., Results: In total, we enrolled 60 patients with KOA and HC who were matched for age, sex, and body mass index (BMI). We found that plasma ccf-mtDNA contents were significantly higher in patients with KOA (median, 2.44; quartile range, 1.10-3.79) than in HC (median, 1.08; quartile range, 0.52-2.12) (P < 0.0001). Plasma ccf-mtDNA content sequentially increased following the KOA class I-IV group (P = 0.040) and positively correlated with the K-L classification (r = 0.369, P = 0.004) and WOMAC scores (r = 0.343, P = 0.007). The ccf-mtDNA content did not significantly differ between patients with bilateral and those with single KOA (P = 0.083). Patients with high levels of ccf-mtDNA had a significantly increased risk of KOA compared with those with low levels of ccf-mtDNA (odds ratio [OR], 4.15, 95% confidence interval [CI], 1.71-10.07; P = 0.002). Quartile analysis revealed a significant dose-dependent association (P trend < 0.001)., Conclusion: Our study's findings showed that plasma ccf-mtDNA was highly expressed in patients with KOA compared with HC. Furthermore, ccf-mtDNA content is significantly associated with the severity and risk of KOA. Therefore, its detection may provide insight into the prevention and treatment of KOA., Competing Interests: Declarations Ethics approval and consent to participate The study was conducted following the principles of the Declaration of Helsinki. This study was approved by the Ethics Committee of the First Affiliated Hospital of Gannan Medical University (approval number: LLSC2023-156) and informed consent was obtained from each participant. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Aim: To compare the differences of choroidal neovascularization (CNV) measurements between swept-source and spectral-domain optical coherence tomography angiography (SS-OCTA and SD-OCTA) in neovascular age-related macular degeneration (nAMD) and the imaging reliability of the two devices., Methods: Prospective comparative study. SS-OCTA and SD-OCTA were used to scan the same eye with the modes of 3×3 and 6×6 mm 2 centered on the neovascularization. Only qualified images were chosen and the border of CNV was manually delineated by two graders independently. The area of CNV (ACNV), vascular perfusion density (PD), and vessel length density (VLD) within the delineation were calculated using Image J. The differences of CNV measurements between the two OCTA devices were compared using Bland-Altman analysis. The agreement between the two graders on the measurements of each device was compared using the intraclass correlation coefficient (ICC)., Results: A total of 18 patients (22 eyes) with nAMD were included. The measurements of ACNV, PD, and VLD were 7.247±4.586 and 4.901±3.741 mm 2 , 43.202±9.636 and 34.904±10.489, 6.339±1.228 and 5.908±1.741 mm -1 for SS-OCTA and SD-OCTA, respectively. The differences between the two devices were 2.346±3.030 mm 2 ( Z =-3.782, P <0.0001), 8.298±14.160 ( Z =-2.419, P =0.016), and 0.431±2.114 mm -1 ( Z =-0.828, P =0.408) for ACNV, PD and VLD, respectively. The ICC between two graders were 0.893 ( P <0.001), 0.902 ( P <0.001), 0.885 ( P <0.001) for ACNV, PD, VLD in SS-OCTA, and 0.971 ( P <0.001), 0.976 ( P <0.001), 0.973 ( P <0.001) in SD-OCTA, respectively., Conclusion: Both OCTA devices have high imaging reliability. Compared with SD-OCTA, SS-OCTA has a larger ACNV measurements, but doesn't show better resolution of internal vessels of CNV and well signal strength., Competing Interests: Conflicts of Interest: Ma JX, None; Zhang ZY, None; Di R, None; Yang JJ, None; Tian SW, None; Qin YZ, None; Zhang WH, None; Lei JQ, None; Liu QP, None; Li JM, None., (International Journal of Ophthalmology Press.)

Background: This study aimed to explore whether cytotoxin-associated gene A (CagA) can inhibit cell cycle progression by activating nuclear factor of activated T cells (NFAT) in lymphoma B cells and contribute to Helicobacter pylori eradication (HPE) responsiveness (complete remission [CR] after HPE) in gastric mucosa-associated lymphoid tissue (MALT) lymphoma., Materials and Methods: We co-cultured three B-lymphoma cell lines (MA-1, OCI-Ly3, and OCI-Ly7) with HP strains (derived from HPE-responsive gastric MALT lymphoma) and evaluated the expression patterns of CagA, phosphorylated (p)-CagA (CagA P-Tyr ), and CagA-signaling molecules, cell-cycle inhibitors, p-NFATc1 (Ser 172 ), and NFATc1 using western blotting. Furthermore, we evaluated the association between nuclear NFATc1 expression in the tumor cells of 91 patients who received first-line HPE (59 patients with HPE responsiveness and 32 without HPE responsiveness) and HPE responsiveness and CagA expression in tumor cells., Results: In HP strains co-cultured with B cell lymphoma cell lines, CagA was translocated to the nucleus through tyrosine phosphorylation (CagA P-Tyr ) and simultaneously dephosphorylated NFATc1, subsequently causing nuclear NFATc1 translocation and stimulating the expression of p-SHP-2/p-ERK/Bcl-xL. Activated NFATc1 causes G1 cell cycle retardation in both MA-1 and OCI-Ly3 cells by triggering p21 and p27 production. Nuclear NFATc1 localization was significantly associated with the presence of CagA in gastric MALT lymphomas (80% [41/51] vs. 33% [13/40]; p < 0.001) and with HPE responsiveness (73% [43/59] vs. 25% [8/32]; p < 0.001). Patients exhibiting both the presence of CagA and nuclear NFATc1 localization responded more rapidly to HPE than those without (median interval to CR, 4.00 vs. 6.00 months, p = 0.003)., Conclusions: Our findings indicated that CagA and NFATc1 cooperatively participate in the lymphomagenesis of HPE-responsive gastric MALT lymphoma., Competing Interests: Declarations Ethics approval and consent to participate The Institutional Review Board of the Research Ethics Committee of National Taiwan University Hospital (approval number: 201801030RINC) approved the study protocol, which included clinical data collection, pathological review, and molecular studies. Consent for publication All listed authors discussed results and commented on the submitted manuscript. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Artificial intelligence (AI) is an interdisciplinary field that combines computer technology, mathematics, and several other fields. Recently, with the rapid development of machine learning (ML) and deep learning (DL), significant progress has been made in the field of AI. As one of the fastest-growing branches, DL can effectively extract features from big data and optimize the performance of various tasks. Moreover, with advancements in digital imaging technology, DL has become a key tool for processing high-dimensional medical image data and conducting medical image analysis in clinical applications. With the development of this technology, the diagnosis of orthopedic diseases has undergone significant changes. In this review, we describe recent research progress on DL in fracture diagnosis and discuss the value of DL in this field, providing a reference for better integration and development of DL technology in orthopedics., Competing Interests: Conflict of Interest Statement The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work., (© 2024. Huazhong University of Science and Technology.)

Background: Skin fibrosis is the typical pathological manifestation of systemic sclerosis (SSc) and localized scleroderma (LS); it has an unclear aetiology and few effective treatments. Although excessive collagen secretion by fibroblasts is the primary cause of skin fibrosis, evidence has suggested that vascular damage is the initiating event and that various cell types, including fibroblasts, work together to contribute to the pathogenesis of skin fibrosis., Objectives: To explore the relationship between vascular endothelial cell lesions and immune cell infiltration, along with the interactions between various cell types within the fibrotic skin ecosystem., Methods: Single-cell RNA sequencing was performed on skin biopsies from three healthy donors and seven patients with SSc. Additional data from three patients with localized scleroderma available in the Gene Expression Omnibus (GSE160536) were integrated by Harmony. CellChat (version 1.5.0) was used to analyse the cell communication network. A Transwell® assay and a bleomycin (BLM) mouse model were used to explore the role of atypical chemokine receptor 1 (ACKR1; 'Duffy antigen') in immune cell infiltration. Milo single-cell Western blot was used to show fibroblast subcluster activation., Results: A total of 62 295 cells were obtained and subpopulations of stromal and immune cells identified. Interaction network analysis found that multiple chemokines secreted by macrophages, pericytes and proinflammatory fibroblasts could bind with ACKR1, which was highly expressed by endothelial cells in lesional skin. The Transwell® assay revealed that overexpression of ACKR1 in human umbilical vein endothelial cells facilitated leucocyte infiltration following treatment with interleukin-8. BLM mice showed enhanced ACKR1 expression, massive immune cell infiltration and skin fibrosis that was attenuated by ACKR1 inhibition. Furthermore, infiltrated macrophages expressing high levels of transforming growth factor (TGF)-β1 or platelet-derived growth factor B (PDGFB) could activate secreted frizzled-related protein 2 (SFRP2)/asporin (ASPN)+ fibroblasts to contribute to the excessive accumulation of extracellular matrix. It was also found that the SOX4-ASPN axis plays an important role in the TGF-β signalling cascade and the aetiology of skin fibrosis., Conclusions: Our results reveal that high expression of ACKR1 by endothelial cells in fibrotic skin tissue promotes immune cell infiltration and that SFRP2/ASPN+ fibroblasts synergize to exacerbate skin fibrosis., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

School bullying occurs frequently in primary and secondary schools, which is a global problem and it often brings serious physical and mental harm to the victims. When school bullying occurs, there may be a large number of bystanders in addition to the bullies and victims. What actions bystanders take affects the progress of school bullying. Relevant studies indicate that social norms including how peers around them react (descriptive norms) and how important adults such as teachers and parents demand (injunctive norms) play important roles in bystanders' action-taking, but limited studies have considered individual differences. Therefore, this study used a person-centered approach to explore the co-existence patterns of social norms and bystanders' defending intention to further understand their relations. We surveyed 1,384 junior high school students in China by self-report questionnaires, and they were asked to assess their defending intention when witnessing school bullying events under different contexts of social norms. Through latent profiles analysis, five co-existing patterns were identified: no norms-no defending group (4.8%), parent norms-no defending group (3.6%), weak norms-low defending group (24.3%), teacher-peer norms-medium defending group (40.6%), teacher-peer norms-high defending group (26.7%). In four out of the five patterns, students' levels of defending intention were highly consistent with the levels of peer and teacher norms, but largely contradicted parent norms. This suggests that descriptive norms from peers and injunctive norms from teachers, other than those from parents are crucial for promoting bystanders' defending intention, which provides important enlightenment for school bullying prevention. These findings provide important enlightenment for the prevention and control of school bullying in the future., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

The receptor tyrosine kinase encoded by the MET gene plays an important role in various cellular processes such as growth, survival, migration and angiogenesis, and its abnormal activation is closely related to the occurrence and development of various tumors. This article reviews the recent advances in diagnosis and treatment of MET-variant digestive tract tumors. In terms of diagnosis, the application of next-generation sequencing technology and liquid biopsy technology makes the detection of MET variants more accurate and efficient, providing a reliable basis for individualized treatment. In terms of treatment, MET inhibitors such as crizotinib and cabotinib have shown good efficacy in clinical trials. In addition, the combination of immunotherapy and MET inhibitors also demonstrated potential synergies, further improving the therapeutic effect. However, the complexity and heterogeneity of drug resistance mechanisms are still one of the difficulties in current research. In the future, it is necessary to further deepen the understanding of the mechanism of MET variation and explore new combination treatment strategies to improve the overall survival rate and quality of life of patients. The diagnosis and treatment of MET-variant digestive tract tumors are moving towards precision and individualization, and have broad application prospects., 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.)

Agarase and its metabolites are reported to have applications in a variety of fields, but there have been few studies of the effects of agaro-oligosaccharide hydrolysate on muscle function. In this study, we analyzed the functionality of agarase and its metabolites in bacteria isolated from seawater. A bacterium with agar-degrading activity was isolated from Shimabara, Nagasaki, Japan. Through 16S rRNA sequence alignment, it was identified as being closely related to Rheinheimera sp. WMF-1 and was provisionally named Rheinheimera sp. (HY). Crude enzymes derived from this bacterium demonstrated an ability to hydrolyze various polysaccharides, including agar, agarose, and starch, with the highest specificity observed for agarose. The optimum pH and temperature were pH 10 and 50 °C. A glycoside bond specificity analysis of enzymatic activity indicated the cleavage of the α-linkage. Next, we investigated the functional effects of agaro-oligosaccharides on C2C12 myotubes. Treatment with 10-30 kDa oligosaccharides significantly increased the hypertrophy rate, diameter, and expression of myosin heavy-chain genes in C2C12 myotubes. These results indicate that the agaro-oligosaccharides produced by the enzymes identified in this study improve muscle mass, suggesting their potential contribution to muscle function.

Cryptococcus neoformans is a widespread fungal pathogen that can infect the human central nervous system (CNS) and cause fungal meningitis, leading to hundreds of thousands of deaths worldwide each year. Previous studies have demonstrated that many signal transduction pathways are crucial for the morphological development and virulence of C. neoformans . In this review, data from over 116 research articles have been compiled to show that many signaling pathways control various characteristics of C. neoformans , individually or in association with other pathways, and to establish strong links among them to better understand C. neoformans pathogenesis. Every characteristic of C. neoformans is closely linked to these signaling pathways, making this a rich area for further research. It is essential to thoroughly explore these pathways to address questions that remain and apply a molecular mechanistic approach to link them. Targeting these pathways is crucial for understanding the exact mechanism of infection pathogenesis and will facilitate the development of antifungal drugs as well as the diagnosis and prevention of cryptococcosis.

Introduction: We investigated the effects of multiple cerebrovascular disease (CeVD) neuroimaging markers on brain functional connectivity (FC), and how such CeVD-related FC changes interact with plasma phosphorylated tau (p-tau)181 (an Alzheimer's disease [AD] marker) to influence downstream neurodegeneration and cognitive changes., Methods: Multivariate associations among four CeVD markers and whole-brain FC in 529 participants across the dementia spectrum were examined using partial least squares correlation. Interactive effects of CeVD-related FC patterns and p-tau181 on longitudinal gray matter volume (GMV) and cognitive changes were investigated using linear mixed-effects models., Results: We identified a brain FC phenotype associated with high CeVD burden across all markers. Further, expression of this general CeVD-related FC phenotype and p-tau181 contributed additively, but not synergistically, to baseline and longitudinal GMV and cognitive changes., Discussion: Our findings suggest that CeVD exerts global effects on the brain connectome and highlight the additive nature of AD and CeVD on neurodegeneration and cognition., Highlights: Effects of multiple cerebrovascular disease (CeVD) markers on functional connectivity were studied. A global network phenotype linked to high burden across CeVD markers was identified. CeVD phenotype and plasma phosphorylated tau 181 contributed additively to downstream outcomes., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background and Aims: This study aimed to evaluate the hemodynamic alterations and right heart remodeling dynamics in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) undergoing treatment with balloon pulmonary angioplasty (BPA)., Methods: This retrospective cohort study involved a cohort of 31 patients with a confirmed diagnosis of CTEPH. Comprehensive clinical evaluations were systematically performed before BPA, and at 3 and 6 months following the procedure., Results: Significant clinical progress was evidenced by the uplift in the percentage of patients achieving WHO-FC II, escalating from 19.35% at baseline to 51.61% at 6 months after BPA ( p  = 0.003). NT-proBNP levels significantly dropped from a median of 614.6 to 69.9 pg/mL ( p  < 0.001). Hemodynamic assessments showed significant decreases in mean PAP from 45.53 ± 11.19 to 22.56 ± 5.81 mmHg ( p  < 0.001) and PVR from 8.33 to 2.86 WU ( p  < 0.001). Echocardiographic analysis revealed substantial reductions in the right atrial area (RAA, from 20.29 ± 7.55 to 16.79 ± 4.82 cm 2 , p  < 0.001) and right ventricular internal diameter (RVID, from 4.13 ± 0.79 to 3.68 ± 0.59 cm, p  = 0.001) at the 3-month interval post-BPA. These improvements were sustained or even enhanced by the 6-month mark, with RAA and RVID further diminishing (to 14.46 ± 3.78 cm 2 and 3.29 ± 0.54 cm, respectively; both p  < 0.01). The TAPSE/PASP ratios showed progressive improvement from baseline (0.32 ± 0.13) to 3 months (0.42 ± 0.13) and continued to improve at 6 months following BPA (0.50 ± 0.11, p  = 0.04 compared to 3 months post-BPA)., Conclusion: BPA has significantly ameliorated clinical conditions, hemodynamic profiles, and initiated a continued reversal in right heart remodeling in patients with CTEPH., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)