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Yang Li,* Qiang Chen,* Hong-Juan Sun, Jian-Hong Zhang, Xuan Liu Pharmaceutical Preparation Section, the Fourth Central Hospital of Tianjin, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang Li, Pharmaceutical preparation section, the Fourth Central Hospital of Tianjin, No. 1, Zhongshan Road, Hebei District, Tianjin, 300142, People’s Republic of China, Tel +86-022-26249316, Email lyg_liyang@yeah.netBackground: Type 2 diabetes mellitus (T2DM) poses a huge threat to population health globally, and more drugs need to be explored for treatment. In this study, we investigated the mechanism of active ingredient catalpol in Rehmannia glutinosa on reduces blood glucose in diabetic.Methods: The T2DM model was constructed by intraperitoneal injection of streptozotocin into Sprague-Dawley (SD) rats, which were randomly grouped into diabetes model group, pioglitazone group, Rehmannia glutinosa group, catalpol high-dose group, catalpol low-dose group and normal control group.The intervention was continued for 28 d, and changes in body weight, fasting blood glucose, insulin and lipid levels were observed.Results: Of all the drugs, pioglitazone had the most pronounced hypoglycemic effect, which began to decline after 2 weeks of treatment in the low-dose catalpol group and had no hypoglycemic effect in the high-dose catalpol group. Among them, Rehmannia glutinosa was able to increase serum triglyceride level, and pioglitazone effectively reduced total cholesterol level in rats. The low dose of catalpol decreased the concentration of low-density lipoprotein cholesterol (LDL), while the high dose of catalpol increased the concentration of LDL.Conclusion: As an active ingredient in Rehmannia glutinosa, catalpol has the potential to lower blood glucose and improve blood lipids in diabetes treatment, and its action may be achieved by regulating the adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, which provides a new idea for the development of new diabetes therapeutic approaches.Keywords: catalpol, Rehmannia glutinosa, type 2 diabetes, traditional Chinese medicine

Hae Jung Sun, Charm Kim, Kibum Park, Sung Jin Lee Department of Ophthalmology, Soonchunhyang University College of Medicine, Soonchunhyang University Hospital, Seoul, South KoreaCorrespondence: Sung Jin LeeDepartment of Ophthalmology, Soonchunhyang University College of Medicine, Soonchunhyang University Hospital, #59 Daesagwan-ro, Yongsan-gu, Seoul 140-743, South KoreaTel +82-2-709-9355Fax +82-2-710-3196Email wismile@schmc.ac.krPurpose: To evaluate the efficacy of a novel snail-tipped exoplant for macular buckling combined with vitrectomy in high myopic eyes with macular hole retinal detachment.Patient and methods: A novel exoplant was simply prepared with a 5 × 3 mm silicone sponge strengthened in the center with a malleable titanium plate. One end was bent to make a rolled tip like a snail shell to be placed under the macula. Combined vitrectomy with macular buckling using this exoplant was performed in eight consecutive cases. The long arm of the exoplant was manipulated manually to fit the curvature of the eyeball and the length was trimmed appropriately after scleral suturing of the exoplant.Results: Retinal reattachment was achieved in all cases (100%) and macular hole closure was confirmed in 6 eyes (75%). The mean best-corrected visual acuity improved from 1.53 ± 0.73 LogMAR preoperatively to 1.14 ± 0.59 LogMAR to postoperatively (p = 0.063). The mean pre- and postoperative AL was 28.44 ± 1.86 mm and 27.60 ± 1.83 mm, respectively (p = 0.016). The mean follow-up period was 15.4 months and no buckle-related complications such as diplopia, infection or exposure of the exoplant were noticed during the period.Conclusion: This exoplant could easily be prepared with readily available materials in the operating room and it was well tolerated with favorable anatomic results in high myopic eyes. Further studies of increased number of patients with long-term follow-up will be necessary.Keywords: exoplant, high myopia, macular buckling, macular hole retinal detachment, posterior staphyloma

Several seemingly unrelated effects in Alcator C-Mod ohmic L-mode plasmas are shown to be closely connected: non-local heat transport, core toroidal rotation reversals, energy confinement saturation and up/down impurity density asymmetries. These phenomena all abruptly transform at a critical value of the collisionality. At low densities in the linear ohmic confinement regime, with collisionality ν* 0.35 (evaluated inside of the q = 3/2 surface), heat transport exhibits non-local behaviour, core toroidal rotation is directed co-current, edge impurity density profiles are up/down symmetric and a turbulent feature in core density fluctuations with kθ up to 15 cm-1 (kθρs ∼ 1) is present. At high density/collisionality with saturated ohmic confinement, electron thermal transport is diffusive, core rotation is in the counter-current direction, edge impurity density profiles are up/down asymmetric and the high k θ turbulent feature is absent. The rotation reversal stagnation point (just inside of the q = 3/2 surface) coincides with the non-local electron temperature profile inversion radius. All of these observations suggest a possible unification in a model with trapped electron mode prevalence at low collisionality and ion temperature gradient mode domination at high collisionality. © 2013 IAEA, Vienna.

Qualitatively novel results on non-locality phenomena in perturbative transport experiments are reported. Here, non-locality means a rapid response in the core follows an edge perturbation on a time scale far shorter than any standard approximation to the global, diffusive model confinement time. Sequential firing of supersonic molecular beam injection on the HL-2A tokamak sustained the increase in the core temperature in response to the edge perturbation. O-mode reflectometers are introduced to measure density fluctuations and show that the central turbulence is suppressed during nonlocallity, suggesting that the interpretation of the phenomenon due to the formation of an 'ITB-like' structure is plausible. ECH switch-off experiments on the HL-2A tokamak demonstrated that the non-local response is sensitive to the deposition location. Taken together, these results suggest that non-locality phenomena have several aspects in common which can be linked to certain simple, generic elements of tokamak turbulence physics. © 2011 IAEA, Vienna.

As a member of the chalcogenide family, NiSe exhibits a direct bandgap of 1.74 eV, making it a promising candidate for nonlinear optical devices. However, its potential in the near-infrared region of the telecommunication band has not been fully explored. In this study, a well-coupled saturable absorber (SA) device is fabricated for the first time using NiSe nanosheets, and it is applied to an ultrafast fiber laser, achieving an ultrashort pulse laser output with an optical conversion efficiency of 13.9%. The laser based on NiSe SA achieves tunable multisoliton mode locking, including conventional solitons, bound-state solitons, dual-wavelength solitons, and second to fourth harmonic solitons, over a wavelength range of 1528.5-1556 nm by adjusting the resonator's polarization state through the polarization controller and controlling the pump power. Numerical simulations and soliton dynamic analysis in the study of NiSe SA reveal the intricate details and behaviors of ultrafast soliton pulse locking. The results indicate that the well-coupled NiSe SA, characterized by a modulation depth of 36.73%, a saturation intensity of 0.287 MW/cm 2 , and excellent spectral broadband absorption properties, can enhance intracavity nonlinear effects and enable the realization of stable and tunable multisoliton mode-locked pulses. Additionally, soliton collisions with group velocity differences are investigated under stable dual-wavelength soliton output, especially vector dual-wavelength soliton. This demonstrates the excellent application potential of NiSe SA in fields such as ultrafast optical communications and information encryption.

Lignocellulosic biomass (LCB) is expected to play a critical role in achieving the goal of biomass-to-bioenergy conversion because of its wide distribution and low price. Biomass fermentation is a promising method for the sustainable generation of biohydrogen (bioH 2 ) from the renewable feedstock. Due to the inherent resistant structure of biomass, LCB needs to be pretreated to improve its digestibility and utilization. However, certain intermediates by-products generated during the pretreatment process, such as phenolic compounds, furan derivatives, and aldehydes, have been identified as potent inhibitors of subsequent anaerobic fermentation due to their disruptive effects on the physiological and metabolic functions of hydrogen-producing microbiota. To counteract the negative effects of these inhibitors on bio-H 2 fermentation, various detoxification strategies for LCB hydrolysates have been explored. This review presents a comprehensive analysis of fermentation-inhibitory by-products commonly generated by modern pretreatment protocols and their negative impacts on biohydrogen fermentation. Furthermore, the underlying mechanisms of inhibition upon hydrogen-producing microbes and their impacts on microbial community dynamics are exhibited. State-of-the-art strategies for detoxifying pretreated LCB have been also discussed, along with alternative pretreatment strategies designed to minimize or eliminate the formation of inhibitory by-products. Additionally, this review addresses the significant gap in the economic viability assessments of these processes, offering a detailed evaluation of both the technological and economic feasibility of biomass fermentation. Given the limitations of previous studies, strategies for cost-effective pretreatment and detoxification should be developed in the future to overcome the inhibition of fermentation inhibitors in the bioconversion of biomass to hydrogen., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

It has been demonstrated that humans exhibit an attention bias towards the lower visual field (e.g., faster target detection for targets appearing below eye level). This bias has been interpreted as reflecting the visual motor demand in near space below eye level. In this study, we examined whether this spatial bias could be affected by participants' hand position at the time of testing. Specifically, if the hand position is held at eye level at the time of target detection, whether the bias toward the lower visual field would be reduced if the bias is directly related to the motor demand at the time of testing. Using a modified spatial cueing paradigm, in Experiment 1, we found a downward bias in reaction time measures and cueing effects in a target detection task. In Experiment 2, using the same stimulus used in Experiment 1, we compared attention performance when participants' dominant (right) hand was positioned close to the right side of the visual display with the conditions where their hand was in their laps. We revealed that despite an influence on the horizontal distribution of attention (lateral peri-hand effect), the downward bias in attention remained regardless of the hand position. This revealed that lateral peri-hand manipulation is insufficient to override the attention advantage for stimuli appearing in the lower visual field., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Myocardial ischemia-reperfusion injury (MIRI) is a complex pathological process that results from the restoration of blood flow to ischemic myocardium, leading to a series of detrimental effects including oxidative stress and inflammation. Stachyose, a naturally occurring oligosaccharide found in traditional Chinese medicinal herbs, has been suggested to possess therapeutic properties against various pathological conditions. However, its impact on MIRI and the underlying mechanisms have not been fully elucidated. In this study, we aimed to investigate the therapeutic effects of stachyose on MIRI and to uncover the molecular mechanisms involved. Using both in vivo and in vitro models of MIRI, we evaluated the effects of stachyose on cardiac function and cell death pathways. Our results indicate that stachyose significantly improves cardiac function and reduces infarct size in MIRI mice. Mechanistically, stachyose modulates the ferroptotic pathway in cardiomyocytes by upregulating the expression of glutathione peroxidase 4 (GPX4) and reducing lipid peroxides and iron levels. Additionally, stachyose inhibits the pyroptotic pathway in macrophages by downregulating the expression of NLRP3, gasdermin D (GSMD-N), and cleaved-caspase-1, leading to decreased levels of proinflammatory cytokines interleukin (IL)-1β and IL-18. This study demonstrates that stachyose exerts a protective effect against MIRI by targeting both ferroptosis and pyroptosis pathways, suggesting its potential as a novel therapeutic agent for the treatment of MIRI. Further research is warranted to explore the detailed mechanisms and therapeutic potential of stachyose in clinical settings., 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 clinical data of 47 children (52 ears) with middle ear cholesteatoma at Eye & ENT Hospital, Fudan University from January 2021 to February 2024 were prospectively collected. There were 30 males and 17 females, with a mean age of (8.5±2.8) years. Surgical procedures included endoscopic tympanoplasty (29 ears), combined endoscopic/microscopic tympanoplasty (8 ears) and microscopic tympanoplasty (15 ears). After endoscopic surgeries, the mean air conduction hearing threshold, mean bone conduction hearing threshold and air bone gap were (28.4±10.4) dB HL, (12.4±5.9) dB HL and (16.0±6.3) dB HL, respectively, which were significantly improved compared with preoperative indicators [(40.2±14.0) dB HL, (16.3±6.8) dB HL and (23.9±9.8) dB HL, respectively] (all P <0.05). There were statistically significant differences in the postoperative mean air conduction hearing threshold and air bone gap among three surgical groups, and the value of endoscope group was lower than those of microscope group and endoscope combined with microscope group (all P <0.05). After a follow-up of 5.6 (1.2, 11.5) months, no statistically significant differences were observed in the rate of successful tympanic membrane healing between endoscope group and microscope group ( P =0.747). One ear in the endoscope group experienced recurrence three years after surgery, and no intracranial and extracranial complications occurred. The current study indicates that endoscopic surgery for pediatric cholesteatoma improves hearing with good results.

The development of a simple drug formulation capable of achieving both activatable type I photoreaction and tumor-responsive release of immunomodulator is crucial for advancing photodynamic immunotherapy (PDIT). Herein, we present a nanostructured photosensitizer (NP5) that is activated by the acidic tumor microenvironment to produce type I reactive oxygen species (ROS) under light irradiation and release the immunomodulator demethylcantharidin (DMC) for PDIT. The NP5 is formed by self-assembly of a versatile phthalocyanine molecule which is composed of DMC and phthalocyanine linked via a pH-responsive amide bond. NP5 produces minimal ROS under light irradiation at the condition of pH 7.4. However, NP5 can release DMC at the condition of pH 6.5 and concurrently trigger type I photoreactions. The results of in vivo experiments indicate that NP5-mediated PDIT induce the increase of cytotoxic T lymphocytes and decrease of regulatory T lymphocytes, which can effectively inhibit the bilateral tumor growth. This work is anticipated to serve as a reference for the development of innovative agents for precise PDIT of hypoxic tumors., Competing Interests: Declaration of competing interest There are no conflicts of interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The extent of rehabilitation of stroke patients outside the hospital is contingent upon their dedication to rehabilitative exercises, adherence to a suitable diet, and medication protocols. Therefore, multiple aspects of compliance must be assessed. Questionnaires are indirect measurements that are economical and easy to use. However, questionnaires should meet specific criteria to minimize errors and ensure reprehensibility of the results., Objective: To develop a new questionnaire-based assessment tool for out-of-hospital treatment adherence in stroke patients and to evaluate the psychometric properties and feasibility of the questionnaire by conducting preliminary measurements in the stroke population. The questionnaire should have at least one validity measure and one reliability measure., Methods: A preliminary "OHAQ-SP" was developed based on a literature review and two rounds of Delphi expert consultation. Between April 1 and July 2022, 308 stroke patients revisited the neurology departments of four Grade A tertiary hospitals in Shanghai using the convenience sampling approach. Various statistical methods, such as item analysis, correlation analysis, exploratory factor analysis, confirmatory factor analysis, and the internal consistency measure Cronbach's α coefficient, were employed to assess the reliability and validity of the questionnaire., Results: A total of 290 questionnaires were collected; the Cronbach's α coefficients were 0.936, 0.862, 0.916, and 0.928 for the different sections, and the overall Cronbach's α coefficient for the entire scale was 0.902. The results of the confirmatory factor analysis were CMIN/DF = 2.490, RMR = 0.05, GFI = 0.901, NFI = 0.927, IFI = 0.955, and RMSEA = 0.054. The standardized loading values varied between 0.717 and 0.916. The combined reliabilities of the four dimensions were 0.936, 0.864, 0.917, and 0.929, respectively. The average variance extraction values for the four dimensions are 0.676, 0.614, 0.611, and 0.652, respectively., Conclusion: The OHAQ-SP is a reliable and accurate instrument for evaluating medication use, nutritional status, and behavior throughout the out-of-hospital rehabilitation phase., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical principles were considered in all stages of the study. Prior to beginning the study, the aim of the study was explained to the individuals who met the inclusion criteria of the study, and written consent from all patients who agreed to participate was obtained using a voluntary informed consent form, which clearly stated that participation in the study was voluntary and that each participant retained the right to refuse to participate in the study or leave at any time. This trial was approved by the Institutional Ethics Committee of the Shanghai Municipal Hospital of TCM (IRB; reference number 2020SHL-KY-16; IRB at the Shanghai Municipal Hospital of TCM Ethics Committee). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

A combined machine learning approach and first-principles calculations are employed to efficiently explore energetically favorable ternary compounds involving Pt and an immiscible Si-Sn pair of elements. We predict two stable Pt-Si-Sn ternary compounds (Pt 2 Si 2 Sn and Pt 8 SiSn 2 ) and reproduce the experimentally synthesized Pt 5 SiSn. The crystal structures of Pt 5 SiSn and Pt 8 SiSn 2 are composed of a SiPt 8 cube and SnPt 12 cuboctahedron. Based on these structural motifs, we design a series of Pt-Si-Sn ternary compounds that contain SiPt 8 and SnPt 12 units and discover some stable and metastable compounds. Partial flat bands near the Fermi level appear in these compounds, and the positions of partial flat bands move upward with increasing the Pt content. The partial flat bands are dominated by Pt atoms. These Pt-Si-Sn ternary compounds provide a platform to study flat band-related properties. Our results open a way to design new compounds in the ternary system.

Integrated fixed-film activated sludge (IFAS) system, an improvement of the activated sludge process, combines the advantages of both attached sludge (AS) and suspended sludge (SS). This study aimed to fully decipher the roles of AS and SS in simultaneous N and P removal in an IFAS system through metagenomic analysis. It was found that AS contributed about 84.04%, 97%, and 95.12% to exogenous NO 3 - -N reduction, endogenous NO 3 - -N reduction, and endogenous NO 2 - -N reduction, respectively. Compared with AS, SS exhibited a greater contribution to anaerobic P release (69.06%) and aerobic P uptake (73.48%). Nitrate and nitrite reductase enzymes showed higher activities in AS, while the activities of exopolyphosphatase and alkaline phosphatase D were more active in SS. P content further indicated that in AS, only a small amount of P was stored in EPS, with most presented intracellularly. In SS, the amount of P stored in EPS was found to be higher. Metagenomic analysis revealed genes related to the synthesis and degradation of endogenous carbon were higher in AS, whereas the TCA cycle exhibited higher activity in SS. P removal-related genes (such as ppk2, ppx, and adk) was significantly higher in SS than in AS. The alteration of genes associated with nitrogen metabolism suggested that the microbes in AS had a higher capacity for nitrification and denitrification. In summary, the discrepancy in the roles of AS and SS in N and P removal in IFAS can be attributed to variations in enzyme activity, P storage in EPS, microbial community composition, and functional gene abundance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Inhibition of return (IOR) is a phenomenon that reflects slower target detection when the target appears at a previously cued rather than uncued location. In the present study, we investigated the extent to which IOR occurs in three-dimensional (3D) scenes comprising pictorial depth information. Peripheral cues and targets appeared on top of 3D rectangular boxes placed on the surface of a textured ground plane in virtual space. When the target appeared at a farther location than the cue, the magnitude of the IOR effect in the 3D condition remained similar to the values found in the two-dimensional (2D) control condition (IOR was depth-blind). When the target appeared at a nearer location than the cue, the magnitude of the IOR effect was significantly attenuated (IOR was depth-specific). The present findings address inconsistencies in the literature on the effect of depth on IOR and support the notion that visuospatial attention exhibits a near-space advantage even in 3D scenes consisting entirely of pictorial depth information., Competing Interests: Declarations. Ethics approval: The study was approved by the McMaster University Research Ethics Board. Consent to participate: Participants completed an informed consent form before starting the experiment. Consent for publication: Participants signed informed consent regarding publishing their data. Open practices statement: None of the data or materials for the experiments reported here are currently available, and none of the experiments were preregistered. Conflicts of interest: All authors declare that they have no conflicts of interest or competing interests to disclose., (© 2024. The Psychonomic Society, Inc.)

Parabacteroides distasonis is a gram-negative bacterium initially isolated from a clinical specimen in the 1930s. The strain was re-classified to form the new genus Parabacteroides in 2006. P. distasonis can regulate intestinal barrier function and plays a key role in immune response and metabolic regulation of bodies. Traditional Chinese medicine(TCM) is closely related to the intestinal microbiota. Polysaccharides, saponins, and other ingredients of TCM can treat diseases by interacting with P. distasonis, but the specific mechanisms underlying these processes are still unclear, requiring further exploration. This study reviewed the roles and related mechanisms of P. distasonis in inflammatory-immune diseases, metabolic diseases, cardiovascular disease, neuropsychiatric diseases, cancer, and other diseases and summarized the relevant research results of TCM to prevent and treat diseases by regulating P. distasonis. This study provides a reference for subsequent exploration of P. distasonis and research on the interaction between TCM and intestinal microbiota.

The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal Parabacteroides goldsteinii (P. goldsteinii) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of P. goldsteinii and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of P. goldsteinii. Our results shed light on the role of intestinal microbiota P. goldsteinii and serum metabolites dodecafluorpentan in CR benefits to AKI., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition., (© 2024. The Author(s).)

A novel room-temperature liquid crystal of tetraphenylethylene derivative (TPE-DHAB) was synthesized using an ionic self-assembly strategy. The TPE-DHAB complex exhibits typical aggregation-induced emission properties and a unique helical supramolecular structure. Moreover, the generation and handedness inversion of circularly polarized luminescence (CPL) can be achieved through further chiral solvation, providing a facile approach to fabricate room-temperature liquid crystalline materials with controllable supramolecular structures and tunable CPL properties through a synergistic strategy of ionic self-assembly and chiral solvation process., (© 2024 Wiley-VCH GmbH.)

Studies have explored how human spatial attention appears allocated in three-dimensional (3D) space. It has been demonstrated that target distance from the viewer can modulate performance in target detection and localization tasks: reaction times are shorter when targets appear nearer to the observer compared to farther distances (i.e., near advantage). Times have reached to quantitatively analyze this literature. In the current meta-analysis, 29 studies (n = 1260 participants) examined target detection and localization across 3-D space. Moderator analyses included: detection vs localization tasks, spatial cueing vs uncued tasks, control of retinal size across depth, central vs peripheral targets, real-space vs stereoscopic vs monocular depth environments, and inclusion of in-trial motion. The analyses revealed a near advantage for spatial attention that was affected by the moderating variables of controlling for retinal size across depth, the use of spatial cueing tasks, and the inclusion of in-trial motion. Overall, these results provide an up-to-date quantification of the effect of depth and provide insight into methodological differences in evaluating spatial attention., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Selection history is widely accepted as a vital source in attention control. Reward history indicates that a learned association captures attention even when the reward is no longer presented, while statistical learning indicates that a learned probability exerts its influence on attentional control (facilitation or inhibition). Existing research has shown that the effects of the reward history and statistical learning are additive, suggesting that these two components influence attention priority through different pathways. In the current study, leveraging the temporal resolution advantages of EEG, we explored whether these two components represent independent sources of attentional bias. The results revealed faster responses to the target at the high-probability location compared to low-probability locations. Both the target and distractor at high-probability locations elicited larger early Pd (50-150 ms) and Pd (150-250 ms) components. The reward distractor slowed the target search and elicited a larger N2pc (180-350 ms). Further, no interaction between statistical learning and the reward history was observed in RTs or N2pc. The different types of temporal progression in attention control indicate that statistical learning and the reward history independently modulate the attention priority map.

Cardiometabolic diseases (CMDs) are major contributors to global mortality, emphasizing the critical need for novel therapeutic interventions. Hydrogen sulfide (H 2 S) has garnered enormous attention as a significant gasotransmitter with various physiological, pathophysiological, and pharmacological impacts within mammalian cardiometabolic systems. In addition to its roles in attenuating oxidative stress and inflammatory response, burgeoning research emphasizes the significance of H 2 S in regulating proteins via persulfidation, a well known modification intricately associated with the pathogenesis of CMDs. This review seeks to investigate recent updates on the physiological actions of endogenous H 2 S and the pharmacological roles of various H 2 S donors in addressing diverse aspects of CMDs across cellular, animal, and clinical studies. Of note, advanced methodologies, including multiomics, intestinal microflora analysis, organoid, and single-cell sequencing techniques, are gaining traction due to their ability to offer comprehensive insights into biomedical research. These emerging approaches hold promise in characterizing the pharmacological roles of H 2 S in health and diseases. We will critically assess the current literature to clarify the roles of H 2 S in diseases while also delineating the opportunities and challenges they present in H 2 S-based pharmacotherapy for CMDs. SIGNIFICANCE STATEMENT: This comprehensive review covers recent developments in H 2 S biology and pharmacology in cardiometabolic diseases CMDs. Endogenous H 2 S and its donors show great promise for the management of CMDs by regulating numerous proteins and signaling pathways. The emergence of new technologies will considerably advance the pharmacological research and clinical translation of H 2 S., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Cichoric acid (CA), a widely utilized polyphenolic compound in medicine, has garnered significant attention due to its potential health benefits. Sepsis-induced acute kidney disease (AKI) is related with an elevated risk of end-stage kidney disease (ESKD). However, it remains unclear whether CA provides protection against septic AKI. The aim of this study is to investigated the protective effect and possible mechanisms of CA against LPS-induced septic AKI. Sepsis-induced AKI was induced in mice through intraperitoneal injection of lipopolysaccharide (LPS), and RAW264.7 macrophages were incubated with LPS. LPS exposure significantly increased the levels of M1 macrophage biomarkers while reducing the levels of M2 macrophage indicators. This was accompanied by the release of inflammatory factors, superoxide anion production, mitochondrial dysfunction, activation of succinate dehydrogenase (SDH), and subsequent succinate formation. Conversely, pretreatment with CA mitigated these abnormalities. CA attenuated hypoxia-inducible factor-1α (HIF-1α)-induced glycolysis by lifting the NAD + /NADH ratio in macrophages. Additionally, CA disrupted the K (lysine) acetyltransferase 2A (KAT2A)/α-tubulin complex, thereby reducing α-tubulin acetylation and subsequently inactivating the NLRP3 inflammasome. Importantly, administration of CA ameliorated LPS-induced renal pathological damage, apoptosis, inflammation, oxidative stress, and disturbances in mitochondrial function in mice. Overall, CA restrained HIF-1α-mediated glycolysis via inactivation of SDH, leading to NLRP3 inflammasome inactivation and the amelioration of sepsis-induced AKI., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterized by chronic inflammation, insulin resistance, and islet cell damage. The prevention of T2DM and its associated complications is an urgent public health issue that affects hundreds of millions of people globally. Numerous studies suggest that disturbances in gut metabolites are important driving forces for the pathogenesis of diabetes. However, the functions and mechanisms of action of most commensal bacteria in T2DM remain largely unknown., Methods: The quantification of bile acids (BAs) in fecal samples was performed using ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). The anti-diabetic effects of Bacteroides uniformis ( B. uniformis ) and its metabolites cholic acid (CA) and chenodeoxycholic acid (CDCA) were assessed in T2DM mice induced by streptozocin (STZ) plus high-fat diet (HFD)., Results: We found that the abundance of B. uniformis in the feces and the contents of CA and CDCA were significantly downregulated in T2DM mice. B. uniformis was diminished in diabetic individuals and this bacterium was sufficient to promote the production of BAs. Colonization of B. uniformis and intragastric gavage of CA and CDCA effectively improved the disorder of glucose and lipid metabolism in T2DM mice by inhibiting gluconeogenesis and lipolysis in the liver. CA and CDCA improved hepatic glucose and lipid metabolism by acting on the Takeda G protein-coupled receptor 5 (TGR5)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway since knockdown of TGR5 minimized the benefit of CA and CDCA. Furthermore, we screened a natural product-vaccarin (VAC)-that exhibited anti-diabetic effects by promoting the growth of B. uniformis in vitro and in vivo. Gut microbiota pre-depletion abolished the favorable effects of VAC in diabetic mice., Conclusions: These data suggest that supplementation of B. uniformis may be a promising avenue to ameliorate T2DM by linking the gut and liver.

Background: Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1β and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction., Purpose: The present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms., Study Design: The palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice., Methods/results: Echocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC., Conclusion: Our findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier GmbH.)

Objective: To assess the infiltration characteristics of tumour-associated macrophages (TAMs) in buccal mucosa carcinoma (BMC) and the correlation of these features with clinicopathological factors., Materials and Methods: Immunohistochemistry was used to detect the expression of TAM-related markers (CD68, CD163, CD206), CD8+ T cell markers, PD-L1, and epidermal growth factor receptor (EGFR) in 46 patients with mucosal cancer after radical surgery. In addition, the correlation between TAM infiltration and clinical characteristics, PD-L1 expression, and EGFR expression was analysed., Results: A high infiltration level of M2-polarized (CD206+) TAMs and M2-polarized (CD163+) TAMs was more common in stage T3-T4, N+, III-IV patients than in other patient groups (P < 0.05). The infiltration degree of M2-polarized (CD68+) TAMs was positively correlated with the PD-L1 TPS (P = 0.0331). The infiltration level of M2-polarized (CD206+) TAMs was higher in the EGFR high expression group than in the EGFR low expression group (P = 0.040)., Conclusion: High infiltration of M2-polarized TAMs is highly associated with advanced disease stage and higher expression of PD-L1 and EGFR in BMCs, suggesting that M2-polarized TAMs infiltration can serve as a potential therapeutic target., (© 2024. The Author(s).)

Ciprofloxacin (CIP) has received considerable attention in recent decades due to its high ecological risk. However, little is known about the potential response of macrophytes and microbes to varying levels of CIP exposure in constructed wetlands. Therefore, lab-scale manganese ore-based tidal flow constructed wetlands (MO-TFCWs) were operated to evaluate the responses of macrophytes and microbes to CIP over the long term. The results indicated that total nitrogen removal improved from 79.93% to 87.06% as CIP rose from 0 to 4 mg L -1 . The chlorophyll content and antioxidant enzyme activities in macrophytes were enhanced under CIP exposure, but plant growth was not inhibited. Importantly, CIP exposure caused a marked evolution of the substrate microbial community, with increased microbial diversity, expanded niche breadth and enhanced cooperation among the top 50 genera, compared to the control (no CIP). Co-occurrence network also indicated that microorganisms may be more inclined to co-operate than compete. The abundance of the keystone bacterium (involved in nitrogen transformation) norank&#95;f&#95;&#95;A0839 increased from 0.746% to 3.405%. The null model revealed drift processes (83.33%) dominated the community assembly with no CIP and 4 mg L -1 CIP. Functional predictions indicated that microbial carbon metabolism, electron transfer and ATP metabolism activities were enhanced under prolonged CIP exposure, which may contribute to nitrogen removal. This study provides valuable insights that will help achieve stable nitrogen removal from wastewater containing antibiotic in MO-TFCWs., 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.)

This study aimed to investigate the relationships among growth mindset, cognitive fusion, bias towards negative information, and bias towards positive information. The Growth Mindset Scale, the Attention to Positive and Negative Information Scale, and the Cognitive Fusion Questionnaire were employed. A total of 470 college students in China participated in the study. The findings showed a negative correlation between a growth mindset and cognitive fusion. In addition, a parallel mediation analysis demonstrated that bias towards negative information mediated the relationship between a growth mindset and cognitive fusion and that the indirect effect was significant. However, the mediation of bias towards positive information in this model was not significant. These results suggest that possessing a growth mindset is advantageous for mental health., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

The integration of electrochemistry with nuclear magnetic resonance (NMR) spectroscopy recently offers a powerful approach to understanding oxidative metabolism, detecting reactive intermediates, and predicting biological activities. This combination is particularly effective as electrochemical methods provide excellent mimics of metabolic processes, while NMR spectroscopy offers precise chemical analysis. NMR is already widely utilized in the quality control of pharmaceuticals, foods, and additives and in metabolomic studies. However, the introduction of additional and external connections into the magnet has posed challenges, leading to signal deterioration and limitations in routine measurements. Herein, we report an anti-interference compact in situ electrochemical NMR system (AICISENS). Through a wireless strategy, the compact design allows for the independent and stable operation of electrochemical NMR components with effective interference isolation. Thus, it opens an avenue toward easy integration into in situ platforms, applicable not only to laboratory settings but also to fieldwork. The operability, reliability, and versatility were validated with a series of biomimetic assessments, including measurements of microbial electrochemical systems, functional foods, and simulated drug metabolisms. The robust performance of AICISENS demonstrates its high potential as a powerful analytical tool across diverse applications.

Microplastics (MPs) pollution has emerged as a global concern, and wastewater treatment plants (WWTPs) are one of the potential sources of MPs in the environment. However, the effect of polyethylene MPs (PE) on nitrogen (N) removal in moving bed biofilm reactor (MBBR) remains unclear. We hypothesized that PE would affect N removal in MBBR by influencing its microbial community. In this study, we investigated the impacts of different PE concentrations (100, 500, and 1000 μg/L) on N removal, enzyme activities, and microbial community in MBBR. Folin-phenol and anthrone colorimetric methods, oxidative stress and enzyme activity tests, and high-throughput sequencing combined with bioinformation analysis were used to decipher the potential mechanisms. The results demonstrated that 1000 μg/L PE had the greatest effect on NH 4 + -N and TN removal, with a decrease of 33.5 % and 35.2 %, and nitrifying and denitrifying enzyme activities were restrained by 29.5-39.6 % and 24.6-47.4 %. Polysaccharide and protein contents were enhanced by PE, except for 1000 μg/L PE, which decreased protein content by 65.4 mg/g VSS. The positive links of species interactions under 1000 μg/L PE exposure was 52.07 %, higher than under 500 μg/L (51.05 %) and 100 μg/L PE (50.35 %). Relative abundance of some metabolism pathways like carbohydrate metabolism and energy metabolism were restrained by 0.07-0.11 % and 0.27-0.4 %. Moreover, the total abundance of nitrification and denitrification genes both decreased under PE exposure. Overall, PE reduced N removal by affecting microbial community structure and species interactions, inhibiting some key metabolic pathways, and suppressing key enzyme activity and functional gene abundance. This paper provides new insights into assessing the risk of MPs to WWTPs, contributing to ensuring the health of aquatic ecosystems., 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 widespread use of microplastics (MPs) has led to an increase in their discharge to wastewater treatment plants. However, the knowledge of impact of MPs on macro-performance and micro-ecology in simultaneous nitrification, denitrification, and phosphorus removal (SNDPR) systems is limited, hampering the understanding of potential risks posed by MPs. This study firstly comprehensively investigated the performance, species interactions, and community assembly under polystyrene (PS) and polyvinyl chloride (PVC) exposure in SNDPR systems. The results showed under PS (1, 10 mg/L) and PVC (1, 10 mg/L) exposure, total nitrogen removal was reduced by 3.38-10.15 %. PS and PVC restrained the specific rates of nitrite and nitrate reduction (SNIRR, SNRR), as well as the activities of nitrite and nitrate reductase enzymes (NIR, NR). The specific ammonia oxidation rate (SAOR) and activity of ammonia oxidase enzyme (AMO) were reduced only at 10 mg/L PVC. PS and PVC enhanced the size of co-occurrence networks, niche breadth, and number of key species while decreasing microbial cooperation by 5.85-13.48 %. Heterogeneous selection dominated microbial community assembly, and PS and PVC strengthened the contribution of stochastic processes. PICRUSt prediction further revealed some important pathways were blocked by PS and PVC. Together, the reduced TN removal under PS and PVC exposure can be attributed to the inhibition of SAOR, SNRR, and SNIRR, the restrained activities of NIR, NR, and AMO, the changes in species interactions and community assembly mechanisms, and the suppression of some essential metabolic pathways. This paper offers a new perspective on comprehending the effects of MPs on SNDPR systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

A limited understanding of microbial interactions and community assembly mechanisms in constructed wetlands (CWs), particularly with different substrates, has hampered the establishment of ecological connections between micro-level interactions and macro-level wetland performance. In this study, CWs with distinct substrates (zeolite, CW&#95;A; manganese ore, CW&#95;B) were constructed to investigate the nutrient removal efficiency, microbial interactions, metabolic mechanisms, and ecological assembly for treating rural sewage with a low carbon-to-nitrogen ratio. CW&#95;B showed higher removal of ammonia nitrogen and total nitrogen by about 1.75-6.75 % and 3.42-5.18 %, respectively, compared to CW&#95;A. Candidatus&#95;Competibacter (denitrifying glycogen-accumulating bacteria) was the dominant microbial genus in CW&#95;A, whereas unclassified&#95;f&#95;Blastocatellaceae (involved in carbon and nitrogen transformation) dominated in CW&#95;B. The null model revealed that stochastic processes (drift) dominated community assembly in both CWs; however, deterministic selection accounted for a higher proportion in CW&#95;B. Compared to those in CW&#95;A, the interactions between microbes in CW&#95;B were more complex, with more key microbes involved in carbon, nitrogen, and phosphorus conversion; the synergistic cooperation of functional bacteria facilitated simultaneous nitrification-denitrification. Manganese ores favour biofilm formation, increase the activity of the electron transport system, and enhance ammonia oxidation and nitrate reduction. These results elucidated the ecological patterns exhibited by microbes under different substrate conditions thereby contributing to our understanding of how substrates shape distinct microcosms in CW systems. This study provides valuable insights for guiding the future construction and management of CWs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Beauvericin (BEA) is a newly identified mycotoxin produced by various Fusarium species, and its contamination in food and animal feed is widespread globally. This mycotoxin demonstrates cytotoxic effects by inducing oxidative stress in multiple models. Furthermore, evidence indicates that BEA possesses diverse toxic activities, making it a promising candidate for toxicological research. Recent studies have highlighted the ability of BEA to traverse the blood-brain barrier, suggesting its potential neurotoxicity. However, limited information is available regarding the neurotoxic effects of BEA on human astrocytes. Therefore, this study aimed to assess the neurotoxic effects of BEA on the Gibco® Human Astrocyte (GHA) cell line and elucidate the underlying mechanisms. Additionally, the study aimed to investigate the protective effects of the antioxidant N-acetylcysteine (NAC) against BEA-induced toxicity. The data show that exposure to BEA within the 2.5-15 μM concentration range resulted in concentration-dependent cytotoxicity. BEA-treated cells exhibited significantly increased levels of reactive oxygen species (ROS), while intracellular glutathione (GSH) content was significantly reduced. Western blot analysis of cells treated with BEA revealed altered protein levels of Bax, cleaved caspase-9, and caspase-3, along with an increased Bax/Bcl-2 ratio, indicating the induction of apoptosis. Additionally, BEA exposure triggered antioxidant responses, as evidenced by increased protein expression of Nrf2, HO-1, and NQO1. Significantly, pretreatment with NAC partially attenuated the significant toxic effects of BEA. In conclusion, our findings suggest that BEA-induced cytotoxicity in GHA cells involves oxidative stress-associated apoptosis. Furthermore, NAC demonstrates potential as a protective agent against BEA-induced oxidative damage., 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.)

This study proposed an efficient framework for optimizing the design and operation of combined systems of wastewater treatment plants (WWTP) and constructed wetlands (CW). The framework coupled a WWTP model with a CW model and used a multi-objective evolutionary algorithm to identify trade-offs between energy consumption, effluent quality, and construction cost. Compared to traditional design and management approaches, the framework achieved a 27 % reduction in WWTP energy consumption or a 44 % reduction in CW cost while meeting strict effluent discharge limits for Chinese WWTP. The framework also identified feasible decision variable ranges and demonstrated the impact of different optimization strategies on system performance. Furthermore, the contributions of WWTP and CW in pollutant degradation were analyzed. Overall, the proposed framework offers a highly efficient and cost-effective solution for optimizing the design and operation of a combined WWTP and CW system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored., Methods: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured., Results: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1., Conclusions: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes., (© 2024. The Author(s).)

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent type of chronic liver disease. However, the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies. Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoetiology and suggest functional therapeutic and diagnostic options. Pyroptosis, ferroptosis, and necroptosis are the main subtypes of non-apoptotic regulated cell deaths (RCDs), each of which represents particular characteristics. Considering the complexity of the findings, the present study aimed to review these types of RCDs and their contribution to NAFLD progression, and subsequently discuss in detail the role of necroptosis in the pathoetiology, diagnosis, and treatment of the disease. The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer, hence it has potential in diagnostic and therapeutic approaches. Nevertheless, further studies are necessary., 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.)

Acetaldehyde dehydrogenase 2 (ALDH2) is a crucial enzyme in alcohol metabolism, and oral administration of ALDH2 is a promising method for alcohol detoxification. However, recombinant ALDH2 is susceptible to hydrolysis by digestive enzymes in the gastrointestinal tract and is expressed as inactive inclusion bodies in E. coli. In this study, we performed three rounds of rational design to address these issues. Specifically, the surface digestive sites of pepsin and trypsin were replaced with other polar amino acids, while hydrophobic amino acids were incorporated to reshape the catalytic cavity of ALDH2. The resulting mutant DE2-852 exhibited a 45-fold increase in soluble expression levels, while its stability against trypsin and pepsin increased by eightfold and twofold, respectively. Its catalytic efficiency (k cat /K m ) at pH 7.2 and 3.2 improved by more than four and five times, respectively, with increased V max and decreased K m values. The enhanced properties of DE2-852 were attributed to the D457Y mutation, which created a more compact protein structure and facilitated a faster collision between the substrate and catalytic residues. These results laid the foundation for the oral administration and mass preparation of highly active ALDH2 and offered insights into the oral application of other proteins., 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 presence of heterotopic ossification (HO) after primary total knee replacement (TKR) is rare and associated with limited mobility and stiffness of the knee. This study aimed to identify if the arthroscopic debridement after TKR could decrease HO and improve the function and range of motion. Thirty HO patients after TKR were retrospectively separated into 2 cohorts. 15 patients of group A accepted the arthroscopic debridement, while 15 patients of group B only had non-operative treatment, mainly including oral nonsteroidal anti-inflammatory drugs (NSAIDs) and rehabilitative treatment. Visual analog scale (VAS) scores, knee society knee scores (KSS), range of motion (knee flexion and knee extension) were obtained before treatment and at 1 month, 3 months, and 6 months after treatment. Radiography of after-treatment was also evaluated to assess the changes in HO. There were 3 males and 27 females with a mean age of 67.4 ± 0.8 years in group A and 68.2 ± 1.3 in group B. The onset time of HO was 3-6 months. The maximum size of the ossification was < 2 cm in 23 knees, 2 cm < heterotopic bone < 5 cm in 6 knees and > 5 cm in 1 knee. The size of HO decreased gradually in all knees by X-ray film at the last follow-up. There were no significant differences in VAS scores after replacement between two groups (p > 0.05). The average range of motion preoperatively in group A was - 15.2-90.6°, which postoperatively increased to - 4.2-110.0°. Meanwhile, the KSS scores and average range of motion of the group A were better than those of the group B at each follow-up time after treatment. Arthroscopic debridement can decrease HO seen from postoperative X-rays, improve the function and range of motion, as well as the pain remission between two groups are comparable. Consequently, arthroscopic resection of HO after TKR is recommended as soon as there is aggravating joint stiffness., (© 2024. The Author(s).)