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Objective: Sarcopenia manifests as a chronic, low-level inflammation along with multiple inflammatory cells infiltration. Interleukin (IL)-25 can regulate the function of macrophages. However, the specific role and mechanisms through which IL-25 functions in sarcopenia are still not fully understood and require further investigation., Methods: Aged mice were utilized as sarcopenia models and examined the expression of inflammatory factors. To investigate the effects of IL-25 on sarcopenia, the model mice received IL-25 treatment and underwent in vivo adoptive transfer of IL-25-induced macrophages. Meanwhile, RAW264.7 cells, bone marrow-derived macrophages, satellite cells and C2C12 cells were used in vitro. Shh insufficiency was induced through intramuscular administration of SHH-shRNA adenoviruses. Then, various assays including scratch wound, cell counting kit-8 and Transwell assays, as well as histological staining and molecular biological methods, were conducted., Results: Aged mice exhibited an accelerated decline in muscle strength and mass, along with an increased muscle lipid droplets and macrophage infiltration, and decreased IL-25 levels compared to the young group. IL-25 therapy and the transfer of IL-25-preconditioned macrophages could improve these conditions by promoting M2 macrophage polarization in vivo as well as in vitro. M2 macrophage conditioned medium enhanced satellite cell proliferation and migration, as well as the vitality, migration, and differentiation of C2C12 cells in vitro. Furthermore, IL-25 enhanced Shh expression in macrophages in vitro, and activated the Shh signaling pathway in muscle tissue of aged mice, which could be suppressed by either the inhibitor cyclopamine or Shh knockdown. Mechanistic studies showed that Shh insufficiency suppressed the activation of Akt/mTOR signaling pathway in muscle tissue of aged mice., Conclusion: IL-25 promotes the secretion of Shh by M2 macrophages and activates the Shh/Akt/mTOR signaling pathway, which improves symptoms and function in sarcopenia mice. This suggests that IL-25 has potential as a therapeutic agent for treating sarcopenia., 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.)

Macrocycles play vital roles in supramolecular chemistry and chromatography. 1,1'-Bi-2-naphthol (BINOL)-based chiral polyimine macrocycles are an emerging class of chiral macrocycles that can be constructed by one-step aldehyde-amine condensation of BINOL derivatives with other building blocks. These macrocycles exhibit good characteristics, such as facile preparation, rigid cyclic structures, multiple chiral centers, and defined molecular cavities, that make them good candidates as new chiral recognition materials for chromatographic enantioseparations. In this study, a BINOL-based [2+2] chiral polyimine macrocycle was synthesized by one-step condensation of enantiopure (S)-2,2'-dihydroxy-[1,1'-binaphthalene]-3,3'-dicarboxaldehyde with (1R,2R)-1,2-diaminocyclohexane. The product was modified with 5-bromo-1-pentene and then attached to thiolated silica using click chemistry to construct a new chiral stationary phase (CSP). The enantioselectivity of the new CSP was explored by separating various racemates under normal phase (NP) and reversed phase (RP) high performance liquid chromatography (HPLC). Thirteen racemates and eight racemates were enantioseparated under the two separation modes, respectively, including chiral alcohols, phenols, esters, ketones, amines, and organic acids. Among them, nine racemates achieved baseline separation under NP-HPLC and seven racemates achieved baseline separation under RP-HPLC. High resolution separation was observed with benzoin (Rs = 5.10), epinephrine (Rs = 4.98), 3-benzyloxy-1,2-propanediol (Rs = 4.42), and 4,4'-dimethylbenzoin (Rs = 4.52) in NP-HPLC, and with 4-methylbenzhydrol (Rs = 4.72), benzoin ethyl ether (Rs = 3.79), 1-phenyl-1-pentanol (Rs = 3.68), and 1-(3-bromophenyl)ethanol (Rs = 3.60) in RP-HPLC. Interestingly, the CSP complemented Chiralcel OD-H, Chiralpak AD-H, and CYCLOBOND I 2000 RSP columns for resolution of these test racemates, separating several racemic compounds that could not be well separated by the three commercially available columns. The influences of injected sample amount on separation were also evaluated. It was found that the column exhibited excellent stability and reproducibility after hundreds of injections, and the relative standard deviations (n = 5) of the retention time and resolution were less than 0.49% and 0.69%, respectively. This study indicates that the BINOL-based chiral macrocycle has great potential for HPLC enantioseparation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Reliable identification of high-risk older adults who are likely to develop sarcopenia is essential to implement targeted preventive measures and follow-up. However, no sarcopenia prediction model is currently available for community use. Our objective was to develop and validate a risk prediction model for calculating the 1-year absolute risk of developing sarcopenia in an aging population., Methods: One prospective population-based cohort of non-sarcopenic individuals aged 60 years or older were used for the development of a sarcopenia risk prediction model and model validation. Sarcopenia was defined according to the 2019 Asian Working Group for Sarcopenia consensus. Stepwise logistic regression was used to identify risk factors for sarcopenia incidence within a 1-year follow-up. Model performance was evaluated using the area under the receiver operating characteristics curve (AUROC) and calibration plot, respectively., Results: The development cohort included 1042 older adults, among whom 87 participants developed sarcopenia during a 1-year follow-up. The PRE-SARC (PREdiction of SARCopenia Risk in community older adults) model can accurately predict the 1-year risk of sarcopenia by using 7 easily accessible community-based predictors. The PRE-SARC model performed well in predicting sarcopenia, with an AUROC of 87% (95% CI, 0.83-0.90) and good calibration. Internal validation showed minimal optimism, with an adjusted AUROC of 0.85. The prediction score was categorized into 4 risk groups: low (0%-10%), moderate (>10%-20%), high (>20%-40%), and very high (>40%). The PRE-SARC model has been incorporated into an online risk calculator, which is freely accessible for daily clinical applications (https://sarcopeniariskprediction.shinyapps.io/dynnomapp/)., Conclusions: In community-dwelling individuals, the PRE-SARC model can accurately predict 1-year sarcopenia incidence. This model serves as a readily available and free accessible tool to identify older adults at high risk of sarcopenia, thereby facilitating personalized early preventive approaches and optimizing the utilization of health care resources., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Objective: Papillary thyroid carcinoma (PTC) is a common malignancy whose incidence is three times greater in females than in males. The prognosis of ageing patients is poor. This research was designed to construct models to predict the overall survival of elderly female patients with PTC., Methods: We developed prediction models based on the random survival forest (RSF) algorithm and traditional Cox regression. The data of 4539 patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Twelve variables were analysed to establish the models. The C-index and the Brier score were selected to evaluate the discriminatory ability of the models. Time-dependent receiver operating characteristic (ROC) curves were also drawn to evaluate the accuracy of the models. The clinical benefits of the two models were compared on the basis of the DCA curve. In addition, the Shapley Additive Explanations (SHAP) plot was used to visualize the contribution of the variables in the RSF model., Results: The C-index of the RSF model was 0.811, which was greater than that of the Cox model (0.781). According to the Brier score and the area under the ROC curve (AUC), the RSF model performed better than the Cox model. On the basis of the DCA curve, the RSF model demonstrated fair clinical benefit. The SHAP plot showed that age was the most important variable contributing to the outcome of PTC in elderly female patients., Conclusions: The RSF model we developed performed better than the Cox model and might be valuable for clinical practice., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Calcitriol (Cal) is the most active metabolite of vitamin D and has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the role of Cal in noise-induced hearing loss (NIHL) to further elucidate the mechanism of noise-induced oxidative stress in the mouse cochlea., Methods: C57BL/6 J mice were given six intraperitoneal injections of Cal (500 ng/kg/d). After 14 days of noise exposure, auditory brainstem response (ABR) thresholds, and the cochlear outer hair cell loss rate were analysed to evaluate auditory function. Real-time fluorescence quantitative PCR, immunofluorescence and western blotting were performed in vitro after the treatment of cochlear explants with 100 µM tert-butyl hydroperoxide (TBHP) for 2.5 h and HEI-OC1 cells with 250 µM TBHP for 1.5 h., Results: In vivo experiments confirmed that Cal pretreatment mitigated NIHL and outer hair cell death. The in vitro results demonstrated that Cal significantly reduced TBHP-induced cochlear auditory nerve fibre degradation and spiral ganglion neuron damage. Moreover, treatment with Cal inhibited the expression of oxidative stress-related factors (3-NT and 4-HNE) and DNA damage-related factors (γ-H2A.X) and attenuated TBHP-induced apoptosis in cochlear explants and HEI-OC1 cells. A total of 1479 upregulated genes and 1443 downregulated genes were screened in cochlear tissue 1 h after noise exposure. The level of transcription factor 3 (ATF3) was significantly elevated in HEI-OC1 cells after TBHP stimulation. Gene Transcription Regulation Database （GTRD）and Cistrome database analyses revealed that the downstream target gene of ATF3 is dual specificity phosphatase 1 (DUSP1). Cistrome DB Toolkit database results showed that the transcription factor of DUSP1 was ATF3. In addition, the ChIP-PCR results indicated that ATF3 might be a direct transcription factor of DUSP1., Conclusion: The results of our study suggest that Cal attenuates NIHL and inhibits noise-induced apoptosis by regulating the ATF3/DUSP1 signalling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Systemic lupus erythematosus (SLE) affects many populations. This study aims to develop a predictive model and create a nomogram for assessing the risk of end-stage renal disease (ESRD) in patients diagnosed with SLE. Data from electronic health records of SLE patients treated at the Affiliated Hospital of North Sichuan Medical College between 2013 and 2023 were collected. The dataset underwent thorough cleaning and variable assignment procedures. Subsequently, variables were selected using one-way logistic regression and lasso logistic regression methods, followed by multifactorial logistic regression to construct nomograms. The model's performance was assessed using calibration, receiver operating characteristic (ROC), and decision curve analysis (DCA) curves. Statistical significance was set at P < 0.05. The predictive variables for ESRD development in SLE patients included anti-GP210 antibody presence, urinary occult blood, proteinuria, white blood cell count, complement 4 levels, uric acid, creatinine, total protein, globulin, glomerular filtration rate, pH, specific gravity, very low-density lipoprotein, homocysteine, apolipoprotein B, and absolute counts of cytotoxic T cells. The nomogram exhibited a broad predictive range. The ROC area under the curve (AUC) was 0.886 (0.858-0.913) for the training set and 0.840 (0.783-0.897) for the testing set, indicating good model performance. The model demonstrated both applicability and significant clinical benefits. The developed model presents strong predictive capabilities and considerable clinical utility in estimating the risk of ESRD in patients with SLE., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

F-P (Fabry-Perot) pressure sensors have a wide range of potential applications in high-temperature, high-pressure, and high-dynamic environments. However, existing demodulation methods commonly rely on spectrometers, which limits their application to high-frequency pressure signal acquisition. To solve this problem, this study developed a self-compensated, three-wavelength demodulation system composite with an F-P pressure sensor and a thermocouple to construct a comprehensive sensing system. The system produces accurate pressure measurements in high-temperature, high-pressure, and high-dynamic environments. In static testing at room temperature, the sensing system shows excellent linearity, and the pressure sensitivity is 158.48 nm/MPa. In high-temperature testing, the sensing system maintains high linearity in the range of 100 °C to 700 °C, with a maximum pressure-indication error of about 0.13 MPa (0~5 MPa). In dynamic testing, the sensor exhibits good response characteristics at 1000 Hz and 5000 Hz sinusoidal pressure frequencies, with a signal-to-noise ratio (SNR) greater than 37 dB and 45 dB, respectively. These results indicate that the sensing system proposed in this study has significant competitive advantages in the field of high-temperature, high-speed, and high-precision pressure measurements and provides an important experimental basis and theoretical support for technological progress in related fields.

The evolution of hypervirulent and carbapenem-resistant Klebsiella pneumoniae can be categorized into three main patterns: the evolution of KL1/KL2-hvKp strains into CR-hvKp, the evolution of carbapenem-resistant K. pneumoniae (CRKp) strains into hv-CRKp, and the acquisition of hybrid plasmids carrying carbapenem resistance and virulence genes by classical K. pneumoniae (cKp). These strains are characterized by multi-drug resistance, high virulence, and high infectivity. Currently, there are no effective methods for treating and surveillance this pathogen. In addition, the continuous horizontal transfer and clonal spread of these bacteria under the pressure of hospital antibiotics have led to the emergence of more drug-resistant strains. This review discusses the evolution and distribution characteristics of hypervirulent and carbapenem-resistant K. pneumoniae, the mechanisms of carbapenem resistance and hypervirulence, risk factors for susceptibility, infection syndromes, treatment regimens, real-time surveillance and preventive control measures. It also outlines the resistance mechanisms of antimicrobial drugs used to treat this pathogen, providing insights for developing new drugs, combination therapies, and a "One Health" approach. Narrowing the scope of surveillance but intensifying implementation efforts is a viable solution. Monitoring of strains can be focused primarily on hospitals and urban wastewater treatment plants., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Fat mass and obesity-associated protein (FTO) is an N6-methyladenosine (m6A) demethylase and plays critical oncogenic roles in multiple cancers. Here we show that FTO is an effective target in hepatocellular carcinoma (HCC). FTO is highly expressed in patients with HCC. Genetic depletion of Fto dramatically attenuated HCC progression in mice. Pharmacological inhibition of FTO by FB23/FB23-2 markedly suppressed the proliferation and migration of HCC cell lines in vitro and inhibited HCC tumorigenicity in xeno-transplanted mice. Mechanistically, FB23-2 suppressed the expression of Erb-b2 receptor tyrosine kinase 3 (ERBB3) and human tubulin beta class Iva (TUBB4A) by increasing the m6A level in these mRNA transcripts. The decrease in ERBB3 expression resulted in the inhibition of Akt-mTOR signaling, which subsequently impaired the proliferation and survival of HCC cells. Moreover, FB23-2 disturbed the stability of the tubulin cytoskeleton, whereas overexpression of TUBB4A rescued the migration of HCC cells. Collectively, our study demonstrates that FTO plays a critical role in HCC by maintaining the proliferation and migration of cells and highlights the potential of FTO inhibitors for targeting HCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Islet transplantation is a promising therapy for patients with type 1 diabetes. However, ischemic injury to the donor islets during cold preservation leads to reduced islet quality and compromises transplant outcome. Several studies imply that liraglutide, a glucagon-like peptide-1 receptor agonist, has a positive effect on promoting islet survival, but its impact on islet cold-ischemic injury remains unexplored. Therefore, the aim of this study was to investigate whether liraglutide can improve islet transplantation efficacy by inhibiting cold-ischemic injury and to explore the underlying mechanisms., Methods: Liraglutide was applied in a mouse pancreas preservation model and a human islets cold-preservation model, and islet viability, function, oxidative stress levels were evaluated. Furthermore, islet transplantation was performed in a syngeneic mouse model and a human-to-nude mouse islet xenotransplantation model., Results: The supplementation of liraglutide in preservation solution improved islet viability, function, and reduced cell apoptosis. Liraglutide inhibited the oxidative stress of cold-preserved pancreas or islets through upregulating the antioxidant enzyme glutathione levels, inhibiting reactive oxygen species accumulation, and maintaining the mitochondrial membrane integrity, which is associated with the activation of Akt signaling. Furthermore, the addition of liraglutide during cold preservation of donor pancreas or donor islets significantly improved the subsequent transplant outcomes in both syngeneic mouse islet transplantation model and human-to-nude mouse islet xenotransplantation model., Conclusions: Liraglutide protects islets from cold ischemia-related oxidative stress during preservation and hence improved islet transplantation outcomes, and this protective effect of liraglutide in islets is associated with the activation of Akt signaling., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Inherent dendrite growth and side reactions of zinc anode caused by its unstable interface in aqueous electrolytes severely limit the practical applications of zinc-ion batteries (ZIBs). To overcome these challenges, a protective layer for Zn anode inspired by cytomembrane structure is developed with PVA as framework and silk fibroin gel suspension (SFs) as modifier. This PVA/SFs gel-like layer exerts similar to the solid electrolyte interphase, optimizing the anode-electrolyte interface and Zn 2+ solvation structure. Through interface improvement, controlled Zn 2+ migration/diffusion, and desolvation, this buffer layer effectively inhibits dendrite growth and side reactions. The additional SFs provide functional improvement and better interaction with PVA by abundant functional groups, achieving a robust and durable Zn anode with high reversibility. Thus, the PVA/SFs@Zn symmetric cell exhibits an ultra-long lifespan of 3150 h compared to bare Zn (182 h) at 1.0 mAh cm -2 -1.0 mAh cm -2 , and excellent reversibility with an average Coulombic efficiency of 99.04% under a large plating capacity for 800 cycles. Moreover, the PVA/SFs@Zn||PANI/CC full cells maintain over 20 000 cycles with over 80% capacity retention under harsh conditions at 5 and 10 A g -1 . This SF-modified protective layer for Zn anode suggests a promising strategy for reliable and high-performance ZIBs., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Maturation of postnatal β cells is regulated in a cell-autonomous manner, and metabolically stressed β cells regress to an immature state, ensuring defective β-cell function and the onset of type 2 diabetes. The molecular mechanisms connecting the nutritional transition to β-cell maturation remain largely unknown. Here, we report a miR-203/ZBTB20/MAFA regulatory axis that mediates the β-cell maturation process. We show that miR-203 level in β cells changes during the nutritional transition and that miR-203 inhibits β-cell maturation at the neonatal stage and under high-fat diet (HFD) conditions. Using single-cell RNA sequencing, we demonstrated that miR-203 elevation promoted the transition of immature β cells into CgBHi endocrine cells, while suppressing gene expressions associated with β-cell maturation in a ZBTB20/MAFA-dependent manner. ZBTB20 is an authentic target of miR-203 and transcriptionally upregulates MAFA expression. Manipulating the miR-203/ZBTB20/MAFA axis may therefore offer a novel strategy for boosting functional β-cell numbers to alleviate diabetes., (© 2024 by the American Diabetes Association.)

Pressure sensors prepared from sapphire exhibit excellent characteristics, including high-temperature resistance, high hardness, and resistance to electromagnetic interference. A Fast Fourier Transform and Mean Square Error (FFT-MSE) demodulation algorithm was employed to demodulate a sapphire sandwich-structure Fabry-Perot (F-P) pressure sensor. Through simulation analysis, the experimental results indicated that the demodulation error of the air cavity length in the range of 206 μm to 216 μm was less than 0.0008%. Compared to single demodulation methods and combined demodulation methods based on FFT or Minimum Mean Square Error (MMSE), the method proposed in this work reduced the demodulation error by more than three times and increased accuracy by more than six times. The algorithm was utilized to demodulate the sapphire sandwich-structure F-P pressure sensor, and the test results indicated that the fitting error of the sensor was less than 0.025% within the pressure range of 0 MPa to 10 MPa. The repeatability error was less than 0.066%, the zero-point deviation was 1.26%, and the maximum stability deviation was 0.0063% per 30 min. The algorithm effectively demodulated the actual cavity length variation in the sapphire sandwich-structure F-P pressure sensor, providing a solution for the performance evaluation of the sapphire sandwich-structure F-P pressure sensor.

Rheumatoid arthritis (RA) involves chronic joint inflammation. Combining acupuncture and medication for RA treatment faces challenges like spatiotemporal variability, limited drug loading in acupuncture needles, and premature or untargeted drug release. Here, we designed a new type of tubular acupuncture needles, with an etched hollow honeycomb-like structure to enable the high loading of therapeutics, integrating the traditional acupuncture and drug repository into an all-in-one therapeutic platform. In these proof-of-concept experiments, we fabricated injectable hollow honeycomb electroacupuncture needles (HC-EA) loaded with melittin hydrogel (MLT-Gel), enabling the combination treatment of acupuncture stimulation and melittin therapy in a spatiotemporally synchronous manner. Since the RA microenvironment is mildly acidic, the acid-responsive chitosan (CS)/sodium beta-glycerophosphate (β-GP)/ hyaluronic acid (HA) composited hydrogel (CS/GP/HA) was utilized to perform acupuncture stimulation and achieve the targeted release of injected therapeutics into the specific lesion site. Testing our therapeutic platform involved a mouse model of RA and bioinformatics analysis. MLT-Gel@HC-EA treatment restored Th17/Treg-mediated immunity balance, reduced inflammatory factor release (TNF-α, IL-6, IL-1β), and alleviated inflammation at the lesion site. This novel combination of modified acupuncture needle and medication, specifically melittin hydrogel, holds promise as a therapeutic strategy for RA treatment., (© 2024. The Author(s).)

Cleanliness has been paramount for municipal solid waste incineration (MSWI) systems. In recent years, the rapid advancement of intelligent technologies has fostered unprecedented opportunities for enhancing the cleanliness of MSWI systems. This paper offers a review and analysis of cutting-edge intelligent technologies in MSWI, which include process monitoring, intelligent algorithms, combustion control, flue gas treatment, and particulate control. The objective is to summarize current applications of these techniques and to forecast future directions. Regarding process monitoring, intelligent image analysis has facilitated real-time tracking of combustion conditions. For intelligent algorithms, machine learning models have shown advantages in accurately forecasting key process parameters and pollutant concentrations. In terms of combustion control, intelligent systems have achieved consistent prediction and regulation of temperature, oxygen content, and other parameters. Intelligent monitoring and forecasting of carbon monoxide and dioxins for flue gas treatment have exhibited satisfactory performance. Concerning particulate control, multi-objective optimization facilitates the sustainable utilization of fly ash. Despite remarkable progress, challenges remain in improving process stability and monitoring instrumentation of intelligent MSWI technologies. By systematically summarizing current applications, this timely review offers valuable insights into the future upgrade of intelligent MSWI 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 Elsevier B.V. All rights reserved.)

There are various indoor fingerprint localization techniques utilizing the similarity of received signal strength (RSS) to discriminate the similarity of positions. However, due to the varied states of different wireless access points (APs), each AP's contribution to RSS similarity varies, which affects the accuracy of localization. In our study, we analyzed several critical causes that affect APs' contribution, including APs' health states and APs' positions. Inspired by these insights, for a large-scale indoor space with ubiquitous APs, a threshold was set for all sample RSS to eliminate the abnormal APs dynamically, a correction quantity for each RSS was provided by the distance between the AP and the sample position to emphasize closer APs, and a priority weight was designed by RSS differences (RSSD) to further optimize the capability of fingerprint distances (FDs, the Euclidean distance of RSS) to discriminate physical distance (PDs, the Euclidean distance of positions). Integrating the above policies for the classical WKNN algorithm, a new indoor fingerprint localization technique is redefined, referred to as FDs' discrimination capability improvement WKNN (FDDC-WKNN). Our simulation results showed that the correlation and consistency between FDs and PDs are well improved, with the strong correlation increasing from 0 to 76% and the high consistency increasing from 26% to 99%, which confirms that the proposed policies can greatly enhance the discrimination capabilities of RSS similarity. We also found that abnormal APs can cause significant impact on FDs discrimination capability. Further, by implementing the FDDC-WKNN algorithm in experiments, we obtained the optimal K value in both the simulation scene and real library scene, under which the mean errors have been reduced from 2.2732 m to 1.2290 m and from 4.0489 m to 2.4320 m, respectively. In addition, compared to not using the FDDC-WKNN, the cumulative distribution function (CDF) of the localization errors curve converged faster and the error fluctuation was smaller, which demonstrates the FDDC-WKNN having stronger robustness and more stable localization performance.

Efficient storage and sharing of massive biomedical data would open up their wide accessibility to different institutions and disciplines. However, compressors tailored for natural photos/videos are rapidly limited for biomedical data, while emerging deep learning-based methods demand huge training data and are difficult to generalize. Here, we propose to conduct Biomedical data compRession with Implicit nEural Function (BRIEF) by representing the target data with compact neural networks, which are data specific and thus have no generalization issues. Benefiting from the strong representation capability of implicit neural function, BRIEF achieves 2[Formula: see text]3 orders of magnitude compression on diverse biomedical data at significantly higher fidelity than existing techniques. Besides, BRIEF is of consistent performance across the whole data volume, and supports customized spatially varying fidelity. BRIEF's multifold advantageous features also serve reliable downstream tasks at low bandwidth. Our approach will facilitate low-bandwidth data sharing and promote collaboration and progress in the biomedical field., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Artificial intelligence (AI) technologies, particularly large language models (LLMs), have been widely employed by the medical community. In addressing the intricacies of urology, ChatGPT offers a novel possibility to aid in clinical decision-making. This study aimed to investigate the decision-making ability of LLMs in solving complex urology-related problems and assess its effectiveness in providing psychological support to patients with urological disorders., Materials and Methods: This study evaluated the clinical and psychological support capabilities of ChatGPT 3.5 and 4.0 in the field of urology. A total of 69 clinical and 30 psychological questions were posed to the AI models, and their responses were evaluated by both urologists and psychologists. As a control, clinicians from Chinese medical institutions provided responses under closed-book conditions. Statistical analyses were conducted separately for each subgroup., Results: In multiple-choice tests covering diverse urological topics, ChatGPT 4.0, performed comparably to the physician group, with no significant overall score difference. Subgroup analyses revealed variable performance, based on disease type and physician experience, with ChatGPT 4.0 generally outperforming ChatGPT 3.5 and exhibiting competitive results against physicians. When assessing the psychological support capabilities of AI, it is evident that ChatGPT4.0 outperforms ChatGPT3.5 across all urology-related psychological problems., Conclusions: The performance of LLMs in dealing with standardized clinical problems and providing psychological support has certain advantages over clinicians. AI stands out as a promising tool for potential clinical aid., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Nitazoxanide (NTZ) is an effective antiparasitic drug with potent antiviral and antimicrobial activity. This randomized, open-label, 2-sequence, 2-period crossover trial was designed to evaluate the bioequivalence (BE) of the NTZ dry suspension in healthy subjects and investigated the effect of food intake on the pharmacokinetic (PK) properties of tizoxanide (an active metabolite of NTZ, TIZ). Sixty healthy Chinese subjects were enrolled and received a single dose of 500 mg/25 mL of preparations on days 1 and 4 under overnight fasting or fed conditions, respectively. The plasma concentration of TIZ was determined using high-performance liquid chromatography/tandem mass spectrometry. PK parameters were calculated using WinNonlin 8.2 and BE was evaluated using SAS 9.4. The 90% confidence intervals for the geometric mean ratio (test/reference) of maximum concentration (C max ), the area under the curve from time 0 to the time of the last quantifiable concentration (AUC 0-t ), and the area under the curve from time 0 to extrapolation to infinity (AUC 0-∞ ) were all within the equivalent interval of 80%-125%, compliant with BE requirements. In comparison with fasting, on taking the reference and test preparations of the NTZ dry suspension after a meal, the AUC 0-t increased by 48.9% and 47.3%, respectively, the AUC 0-∞ increased by 48.4% and 48.3%, respectively, and the post-meal T max was prolonged by 1.8-2 hours. Our results demonstrate that the test and reference preparations were bioequivalent. High-fat meals significantly improve the degree of drug absorption and delay the rate of drug absorption., (© 2024, The American College of Clinical Pharmacology.)

Background: Diabetes is an independent risk factor for mesh complications in women undergoing mesh-augmented surgical repairs of stress urinary incontinence and/or pelvic organ prolapse. The underlying mechanism remains unclear., Objective: This study aimed to define the diabetes-associated alterations in the host inflammatory response to mesh and correlate them with perioperative glucose management., Study Design: Deidentified demographics and medical records of patients who underwent mesh removal and participated in a mesh biorepository study were reviewed (n=200). In patients with diagnosed diabetes (n=25), blood glucose management before initial mesh implantation and before and after mesh removal was assessed by blood glucose and hemoglobin A1c levels. Age- and body mass index-matched tissue samples excised from patients with and without diabetes were examined. Transcriptomic profiles of immune cell markers, immune mediators, key inflammatory regulators, cell senescence, and epigenetic enzymes were determined by multiplex transcriptomic assays (NanoString). Ratios of apoptotic cells to CD68+ macrophages were examined with immunofluorescence. Protein profiles of 12 molecules involved in apoptotic cell clearance were examined with a multiplex protein assay (Luminex)., Results: Demographic and clinical characteristics, including duration between mesh implantation and removal, reason for removal, and type of mesh, etc., were comparable between patients with and without diabetes, except for 11.6% higher body mass index in the former (P=.005). In patients with diabetes, suboptimal management of blood glucose following mesh implantation was observed, with 59% of the patients having loosely or poorly controlled glucose before and after the mesh removal. Ongoing chronic inflammatory response was observed in the excised mesh-tissue complexes in both groups, whereas markers for M2 macrophages (Mrc1 [mannose receptor C-type 1]) and helper T cells (Cd4 [CD4 molecule]) were increasingly expressed in the diabetic vs nondiabetic group (P=.023 and .047, respectively). Furthermore, the gene expressions of proinflammatory Ccl24 (C-C motif chemokine ligand 24) and Ccl13 (C-C motif chemokine ligand 13) were upregulated by 1.5- and 1.8-fold (P=.035 and .027, respectively), whereas that of Il1a (interleukin 1 alpha) was paradoxically downregulated by 2.2-fold (P=.037) in the diabetic vs nondiabetic group. Interestingly, strong positive correlations were found between the expression of Ccl13, Setdb2 (SET domain bifurcated histone lysine methyltransferase 2), and M2 macrophage markers, and between the expression of Il1a, Fosl1 (activator protein-1 transcription factor subunit), and dendritic cell markers, suggesting the involvement of macrophages and dendritic cells in the diabetes-dysregulated proinflammatory response. Supportively, apoptotic cell clearance, which is an important function of macrophages, appeared to be impaired in the diabetic group, with a significantly increased protein level of CALR (calreticulin), an "eat-me" signal on the surface of apoptotic cells (P=.031), along with an increase of AXL (AXL receptor tyrosine kinase) (P=.030), which mediates apoptotic cell clearance., Conclusion: Diabetes was associated with altered long-term inflammatory response in complicated mesh implantation, particularly involving innate immune cell dysfunction. Suboptimal blood glycemic control following mesh implantation may contribute to this immune dysregulation, necessitating further mechanistic studies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

It was common to see that older adults were reluctant to be vaccinated for coronavirus disease 2019 (COVID-19) in China. There is a lack of practical prediction models to guide COVID-19 vaccination program. A nationwide, self-reported, cross-sectional survey was conducted from September 2022 to November 2022, including people aged 60 years or older. Stratified random sampling was used to divide the dataset into derivation, validation, and test datasets at a ratio of 6:2:2. Least absolute shrinkage and selection operator and multivariable logistic regression were used for variable screening and model construction. Discrimination and calibration were assessed primarily by area under the receiver operating characteristic curve (AUC) and calibration curve. A total of 35057 samples (53.65% males and mean age of 69.64 ± 7.24 years) were finally selected, which constitutes 93.73% of the valid samples. From 33 potential predictors, 19 variables were screened and included in the multivariable logistic regression model. The mean AUC in the validation dataset was 0.802, with sensitivity, specificity, and accuracy of 0.732, 0.718 and 0.729 respectively, which were similar to the parameters in the test dataset of 0.755, 0.715 and 0.720, respectively, and the mean AUC in the test dataset was 0.815. There were no significant differences between the model predicted values and the actual observed values for calibration in these groups. The prediction model based on self-reported characteristics of older adults was developed that could be useful for predicting the willingness for COVID-19 vaccines, as well as providing recommendations in improving vaccine acceptance.

Ethnopharmacological Relevance: Da-yuan-yin decoction (DYY) is a classical traditional Chinese medicine prescription for ulcerative colitis (UC)., Aim of Study: This study explored the protective effects and mechanisms of DYY on UC., Materials and Methods: The mice were fed 2.5% dextran sulfate sodium (DSS) for 7 days to establish UC. On the second day, DYY (0.4 g/kg, 0.8 g/kg, 1.6 g/kg) was orally administered daily for 7 consecutive days. The colon tissues and serum were measured by histopathological examination and biochemical analysis., Results: DYY significantly reduced the disease activity index (DAI) and severity of colon shortening and alleviated pathological changes in the colon tissue. DYY restored the protein expression of intestinal tight junction (TJ) protein (ZO-1, occludin and claudin-3). DYY remarkably decreased the level of lipopolysaccharide (LPS), Lactic acid (LA), circulating free DNA (cfDNA), complement (C3, C3a, C3c, C3aR1, C5a and C5aR1) and regulated the levels of inflammatory cytokines in serum. DYY significantly inhibited the expressions of nuclear factor kappa-B p65 (NF-κB p65) and Toll-like receptor 4 (TLR4), citrullinated histone H3 (CitH3) and myeloperoxidase (MPO), reactive oxygen species (ROS) peptidylarginine deiminase 4 (PAD4) and CD 11b, the mRNA levels of PADI4, MPO and ELANE in colon tissues., Conclusions: DYY significantly attenuated DSS-induced UC, which was related with regulating the inflammatory response by the inhibition of complement activation, the LPS-TLR4/NF-κB signaling pathway and neutrophil extracellular traps (NETs) formation. DYY is a potential therapeutic agent for UC., 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.)

Introduction: Comparative studies on surgical treatments with time-to-event endpoints have provided substantial evidence for clinical practice, but the accurate use of survival data analysis and the control of confounding bias remain big challenges., Methods: This was a survey of surgical studies with survival outcomes published in four general medical journals and five general surgical journals in 2021. The two most concerned statistical issues were evaluated, including confounding control by propensity score analysis (PSA) or multivariable analysis and testing of proportional hazards (PH) assumption in Cox model., Results: A total of 74 studies were included, comprising 63 observational studies and 11 randomized controlled trials. Among the observational studies, the proportion of studies utilizing PSA in surgical oncology and non-oncology studies was similar (40.9 % versus 36.8 %, P = 0.762). However, the former reported a significantly lower proportion of PH assumption assessments compared to the latter (13.6 % versus 42.1 %, P = 0.020). Twenty-five observational studies (25/63) used PSA methods, but two-thirds of them (17/25) showed unclear balance of baseline data after PSA. And the proportion of PH assumption testing after PSA was slightly lower than that before PSA, but the difference was not statistically significant (24.0 % versus 28.0 %, P = 0.317). Comprehensive suggestions were given on confounding control in survival analysis and alternative resolutions for non-compliance with PH assumption., Conclusion: This study highlights suboptimal reporting of PH assumption evaluation in observational surgical studies both before and after PSA. Efforts and consensus are needed with respect to the underlying assumptions of statistical methods., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Ethnopharmacological Relevance: Cynanchum otophyllum C.K.Schneid.PI.Wilson, commonly referred as ''Qingyangshen'' (QYS), is a traditional folk medicine from Yunnan, renowned for its efficacy in neurological and psychiatric disorders. Glycosides isolated from QYS have shown promise in alleviating epilepsy, however, mechanisms of action and specific molecular targets remain to be elucidated., Aim of the Study: The study aimed to evaluate the anticonvulsant effects of Qingyangshen glycosides M1 (M1), a C 21 steroidal glycoside from QYS, on pentylenetetrazol (PTZ)-induced convulsions in zebrafish (Danio rerio), and its neuroprotective effect on Glutamate (Glu)-induced damage to PC12 cells, and importantly to identify its potential molecular targets., Materials and Methods: To evaluate anticonvulsant activity of M1, 7 days-post-fertilization (7-dpf) animals were pretreated (by immersion) and then exposed to PTZ (10 mM) solution. Furthermore, Glu-induced PC12 cell damage was employed to investigate the neuroprotective and anti-apoptotic capacity. Cells were pretreated with various concentrations of M1 (0-10 μM) for 12 h and then co-treated with Glu (15 mM) for an additional 24 h. The cell viability, apoptosis rate and apoptosis-related proteins (p-PI3K, PI3K, Akt, p-Akt, CREB, p-CREB, BDNF, Bax and Bcl-2) were measured using CCK-8, annexin V/PI and Western blot assays. To model the expected interaction between M1 and candidate cannabinoid receptor type 1 (CB 1 R), ERK phosphorylation, molecular docking, and drug affinity responsive target stability (DARTS) techniques were employed. Finally, CB 1 R antagonist Rimonabant (Rim) was validated by co-administration in both zebrafish and cells to confirm the requirement of CB 1 R for M1 efficacy., Results: At a concentration of 400 μM, M1 dramatically reversed PTZ-induced convulsive-like behaviors in zebrafish, as evidenced by a significant reduction in locomotor activity. In the context of Glu-induced cytotoxicity, M1 (10 μM) demonstrated a notable increase in cell viability and suppressed apoptosis through modulation of the Bax/Bcl-2 ratio and activation of the PI3K/Akt/CREB/BDNF signaling axis. These effects were facilitated through CB 1 R activation. In contrast, Rim dampened the beneficial activities of M1 as a cannabinoid agonist., Conclusions: These results demonstrated that M1 as a potential CB 1 R activator, exhibiting anticonvulsive effects in a PTZ-induced zebrafish model and neuroprotective properties via the PI3K/Akt/CREB/BDNF signaling axis in a Glu-induced PC12 cell injury model. Notably, the observed seizure relief attenuated by CB 1 R chemical antagonism., 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.)

Sarcopenia is a significant geriatric syndrome that involves the loss of skeletal muscle mass and strength. Due to its substantial endocrine role, the metabolic microenvironment of skeletal muscle undergoes changes with age. Examining the pathogenesis of sarcopenia through focusing on metabolic dysregulation could offer insights for developing more effective intervention strategies. In this study, we analyzed the transcriptomics data to identify specific genes involved in the regulation of metabolism in skeletal muscle during the development of sarcopenia. Three machine learning algorithms were employed to screen key target genes exhibiting strong correlations with metabolism, which were further validated using RNA-sequencing data and publicly accessible datasets. Among them, the metabolic enzyme nicotinamide N-methyltransferase (NNMT) was elevated in sarcopenia, and predicted sarcopenia with an area under the curve exceeding 0.7, suggesting it as a potential therapeutic target for sarcopenia. As expected, inhibition of NNMT improved the grip strength in aging mice and alleviated age-related decline in the mass index of the quadriceps femoris muscles and whole-body lean mass index. Additionally, the NNMTi treatment increased the levels of nicotinamide adenine dinucleotide (NAD + ) content, as well as PGC1α and p-AMPK expression in the muscles of both the D-galactose-treated mouse model and naturally aging mouse model. Overall, this work demonstrates NNMT as a promising target for preventing age-related decline in muscle mass and strength., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: The rise of artificial intelligence (AI) in medicine has revealed the potential of ChatGPT as a pivotal tool in medical diagnosis and treatment. This study assesses the efficacy of ChatGPT versions 3.5 and 4.0 in addressing renal cell carcinoma (RCC) clinical inquiries. Notably, fine-tuning and iterative optimization of the model corrected ChatGPT's limitations in this area., Methods: In our study, 80 RCC-related clinical questions from urology experts were posed three times to both ChatGPT 3.5 and ChatGPT 4.0, seeking binary (yes/no) responses. We then statistically analyzed the answers. Finally, we fine-tuned the GPT-3.5 Turbo model using these questions, and assessed its training outcomes., Results: We found that the average accuracy rates of answers provided by ChatGPT versions 3.5 and 4.0 were 67.08% and 77.50%, respectively. ChatGPT 4.0 outperformed ChatGPT 3.5, with a higher accuracy rate in responses (p < 0.05). By counting the number of correct responses to the 80 questions, we then found that although ChatGPT 4.0 performed better (p < 0.05), both versions were subject to instability in answering. Finally, by fine-tuning the GPT-3.5 Turbo model, we found that the correct rate of responses to these questions could be stabilized at 93.75%. Iterative optimization of the model can result in 100% response accuracy., Conclusion: We compared ChatGPT versions 3.5 and 4.0 in addressing clinical RCC questions, identifying their limitations. By applying the GPT-3.5 Turbo fine-tuned model iterative training method, we enhanced AI strategies in renal oncology. This approach is set to enhance ChatGPT's database and clinical guidance capabilities, optimizing AI in this field., (© 2024. Society of Surgical Oncology.)

Background: Eukaryotic genes contain introns that are removed by the spliceosomal machinery during mRNA maturation. Introns impose a huge energetic burden on a cell; therefore, they must play an essential role in maintaining genome stability and/or regulating gene expression. Many genes (> 50%) in Plasmodium parasites contain predicted introns, including introns in 5' and 3' untranslated regions (UTR). However, the roles of UTR introns in the gene expression of malaria parasites remain unknown., Methods: In this study, an episomal dual-luciferase assay was developed to evaluate gene expression driven by promoters with or without a 5'UTR intron from four Plasmodium yoelii genes. To investigate the effect of the 5'UTR intron on endogenous gene expression, the pytctp gene was tagged with 3xHA at the N-terminal of the coding region, and parasites with or without the 5'UTR intron were generated using the CRISPR/Cas9 system., Results: We showed that promoters with 5'UTR introns had higher activities in driving gene expression than those without 5'UTR introns. The results were confirmed in recombinant parasites expressing an HA-tagged gene (pytctp) driven by promoter with or without 5'UTR intron. The enhancement of gene expression was intron size dependent, but not the DNA sequence, e.g. the longer the intron, the higher levels of expression. Similar results were observed when a promoter from one strain of P. yoelii was introduced into different parasite strains. Finally, the 5'UTR introns were alternatively spliced in different parasite development stages, suggesting an active mechanism employed by the parasites to regulate gene expression in various developmental stages., Conclusions: Plasmodium 5'UTR introns enhance gene expression in a size-dependent manner; the presence of alternatively spliced mRNAs in different parasite developmental stages suggests that alternative slicing of 5'UTR introns is one of the key mechanisms in regulating parasite gene expression and differentiation., (© 2024. The Author(s).)

Alzheimer's disease (AD) is an important public health challenge with a limited understanding of its pathogenesis. Smoking is a significant modifiable risk factor for AD progression, and its specific mechanism is often interpreted from a toxicological perspective. However, microbial infections also contribute to AD, with oral microbiota playing a crucial role in its progression. Notably, smoking alters the ecological structure and pathogenicity of the oral microbiota. Currently, there is no systematic review or summary of the relationship between these three factors; thus, understanding this association can help in the development of new treatments. This review summarizes the connections between smoking, AD, and oral microbiota from existing research. It also explores how smoking affects the occurrence and development of AD through oral microbiota, and examines treatments for oral microbiota that delay the progression of AD. Furthermore, this review emphasizes the potential of the oral microbiota to act as a biomarker for AD. Finally, it considers the feasibility of probiotics and oral antibacterial therapy to expand treatment methods for AD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cough is a common symptom that affects patients' recovery and quality of life after esophagectomy. This study sought to investigate trends in postoperative cough and the factors that influence cough., Methods: A total of 208 of 225 patients were enrolled in this study. The Mandarin Chinese version of the Leicester Cough Questionnaire was administered the day before surgery and at three time points (1 week, 1 month, and 3 months) after esophagectomy to assess patient-reported outcomes., Results: All patients' LCQ-MC scores after surgery were lower than presurgery (P < 0.05), with the lowest score found 1 week after esophagectomy. Factors associated with a cough 1 week after surgery included clinical stage of cancer (OR 0.782, 95% CI 0.647-0.944, P = 0.011), anastomotic position (OR 1.241, 95% CI 1.069-1.441, P = 0.005), duration of surgery (OR 0.759, 95% CI 0.577-0.998, P = 0.049), and subcarinal lymph node dissection (OR 0.682, 95% CI 0.563-0.825, P < 0.001). Factors associated with a cough one month after surgery included clinical stage (OR 0.782, 95% CI 0.650-0.940, P = 0.009), anastomotic position (OR 1.293, 95% CI 1.113-1.503, P = 0.001), and maintaining a semi-reclining position (OR 1.440, 95% CI 1.175-1.766, P < 0.001). Factors associated with a cough 3 months after surgery were clinical stage (OR 0.741, 95% CI 0.591-0.928, P = 0.009) and anastomotic position (OR 1.220, 95% CI 1.037-1.435, P = 0.016)., Conclusions: This study showed that the factors influencing postoperative cough differed over time following esophagectomy. These results may warrant prospective intervention to better manage patients undergoing surgery for esophageal cancer to prevent postoperative cough., (© 2024. The Author(s).)

Background and Objective: Combinations of immune checkpoint inhibitors and nab-paclitaxel have achieved significant therapeutic effects in the treatment of advanced urothelial carcinoma. Our aim was to assess the efficacy and safety of tislelizumab combined with low-dose nab-paclitaxel in patients with muscle-invasive bladder cancer (MIBC)., Methods: TRUCE-01 was a single-arm phase 2 study that included 62 patients with T2-4a N0/X M0 MIBC tumors with predominant urothelial carcinoma histology. Eligible patients received three 21-d cycles of intravenous 200 mg tislelizumab on day 1 plus intravenous 200 mg nab-paclitaxel on day 2, followed by surgical assessment. The primary study endpoint was a clinical complete response (cCR). Treatment-related adverse event (TRAE) profiles were recorded according to Common Terminology Criteria for Adverse Events version 5.0., Key Findings and Limitations: The safety analysis included all 62 patients and the efficacy analysis included 48 patients. The primary efficacy endpoint (cCR) was met by 25 patients (52%) patients. Among the 62 patients in the safety analysis, six (9.7%) had grade ≥3 TRAEs., Conclusions: Tislelizumab combined with low-dose nab-paclitaxel showed promising antitumor effectiveness and was generally well tolerated, which makes it an excellent preoperative therapy option for MIBC., Patient Summary: We found that a combination of the drugs tislelizumab and low-dose nab-paclitaxel had satisfactory efficacy and safety for preoperative treatment of muscle-invasive bladder cancer., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Feline parvovirus (FPV) infection is highly fatal in felines. NS1, which is a key nonstructural protein of FPV, can inhibit host innate immunity and promote viral replication, which is the main reason for the severe pathogenicity of FPV. However, the mechanism by which the NS1 protein disrupts host immunity and regulates viral replication is still unclear. Here, we identified an FPV M1 strain that is regulated by the NS1 protein and has more pronounced suppression of innate immunity, resulting in robust replication. We found that the neutralization titer of the FPV M1 strain was significantly lower than that of the other strains. Moreover, FPV M1 had powerful replication ability, and the FPV M1-NS1 protein had heightened efficacy in repressing interferon-stimulated genes (ISGs) expression. Subsequently, we constructed an FPV reverse genetic system, which confirmed that the N588 residue of FPV M1-NS1 protein is a key amino acid that bolsters viral proliferation. Recombinant virus containing N588 also had stronger ability to inhibit ISGs, and lower ISGs levels promoted viral replication and reduced the neutralization titer of the positive control serum. Finally, we confirmed that the difference in viral replication was abolished in type I IFN receptor knockout cell lines. In conclusion, our results demonstrate that the N588 residue of the NS1 protein is a critical amino acid that promotes viral proliferation by increasing the inhibition of ISGs expression. These insights provide a reference for studying the relationship between parvovirus-mediated inhibition of host innate immunity and viral replication while facilitating improved FPV vaccine production.IMPORTANCEFPV infection is a viral infectious disease with the highest mortality rate in felines. A universal feature of parvovirus is its ability to inhibit host innate immunity, and its ability to suppress innate immunity is mainly accomplished by the NS1 protein. In the present study, FPV was used as a viral model to explore the mechanism by which the NS1 protein inhibits innate immunity and regulates viral replication. Studies have shown that the FPV-NS1 protein containing the N588 residue strongly inhibits the expression of host ISGs, thereby increasing the viral proliferation titer. In addition, the presence of the N588 residue can increase the proliferation titer of the strain 5- to 10-fold without affecting its virulence and immunogenicity. In conclusion, our findings provide new insights and guidance for studying the mechanisms by which parvoviruses suppress innate immunity and for developing high-yielding FPV vaccines., Competing Interests: The authors declare no conflict of interest.

Selenium (Se) is an essential trace element for biological processes. Seleno-amino acids (Se-AAs), known as the organic forms of Se, and their metabolic reprogramming have been increasingly recognized to regulate antioxidant defense, enzyme activity, and tumorigenesis. Therefore, there is emerging interest in exploring the potential application of Se-AAs in antitumor therapy. In addition to playing a vital role in inhibiting tumor growth, accumulating evidence has revealed that Se-AA metabolism could reshape the tumor microenvironment (TME) and enhance immunotherapy responses. This review presents a comprehensive overview of the current progress in multifunctional Se-AAs for antitumor treatment, with a particular emphasis on elucidating the crosstalk between Se-AA metabolism and various cell types in the TME, including tumor cells, T cells, macrophages, and natural killer cells. Furthermore, novel applications integrating Se-AAs are also discussed alongside prospects to provide new insights into this emerging field., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: Increased expression of leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) is associated with immune evasion in breast cancer (BC). The aim of this study to elucidate the role of LILRB2 in BC progression., Methods: LILRB2 expression in tumor tissues was detected by immunohistochemical staining. Human leukocyte antigen A (HLA-A) expression in BC cells was detected by Western blotting, and HLA-A ubiquitination was detected by immunoprecipitation and histidine pulldown assay. An in-situ tumor model was established in nude BALB/c mice to verify the role of LILRB2 in immune escape. Finally, the functions and potential mechanisms of LILRB2 in BC progression were explored using in silico data., Results: LILRB2 was upregulated in BC tissues and cells, and correlated positively with poor prognosis. LILRB2 promoted BC progression by downregulating HLA-A expression. Mechanistically, LILRB2 facilitates the ubiquitination and subsequent degradation of HLA-A by promoting the interaction between the ubiquitin ligase membrane-associated ring finger protein 9 (MARCH9) and HLA-A. In syngeneic graft mouse models, LILRB2-expressing BC cells evaded CD8 + T cells and inhibited the secretion of cytokines by the cytotoxic CD8 + T cells., Conclusion: LILRB2 downregulates HLA-A to promote immune evasion in BC cells and is a promising new target for BC treatment., (© 2024. Springer Nature Switzerland AG.)

Background: During the use of electronic cigarettes (e-cigarettes), users are still exposed to carcinogens similar to those found in tobacco products. Since these carcinogens are metabolized and excreted in urine, they may have carcinogenic effects on the bladder urinary tract epithelium. This meta-analysis aimed to compare bladder cancer carcinogens in the urine of tobacco users and e-cigarette users using a large number of samples., Methods: A systematic meta-analysis was performed using data obtained from several scientific databases (up to November 2023). This cumulative analysis was performed following the Preferred Reporting Items for Systematic Evaluation and Meta-Analysis (PRISMA) and Assessing the Methodological Quality of Systematic Evaluations (AMSTAR) guidelines, according to a protocol registered with PROSPERO. This study was registered on PROSPERO and obtained the unique number: CRD42023455600., Results: The analysis included 10 high-quality studies that considered polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) and tobacco-specific nitrosamines (TSNAs). Statistical indicators show that there is a difference between the tobacco user group and the e-cigarette user group in terms of 1-Hydroxynaphthalene (1-NAP) [weighted mean difference (WMD)10.14, 95% confidence interval (CI) (8.41 to 11.88), p < 0.05], 1-Hydroxyphenanthrene (1-PHE) [WMD 0.08, 95% CI (-0.14 to 0.31), p > 0.05], 1-Hydroxypyrene (1-PYR) [WMD 0.16, 95% CI (0.12 to 0.20), p < 0.05], 2-Hydroxyfluorene (2-FLU) [WMD 0.69, 95% CI (0.58 to 0.80), p < 0.05], 2-Hydroxynaphthalene (2-NAP) [WMD 7.48, 95% CI (4.15 to 10.80), p < 0.05], 3-Hydroxyfluorene (3-FLU) [WMD 0.57, 95% CI (0.48 to 0.66), p < 0.05], 2-Carbamoylethylmercapturic acid (AAMA) [WMD 66.47, 95% CI (27.49 to 105.46), p < 0.05], 4-Hydroxy-2-buten-1-yl-mercapturic acid (MHBMA) [WMD 287.79, 95% CI (-54.47 to 630.04), p > 0.05], 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL) [WMD 189.37, 95% CI (78.45 to 300.29), p < 0.05], or N0-nitrosonornicotine (NNN) [WMD 11.66, 95% CI (7.32 to 16.00), p < 0.05]., Conclusion: Urinary bladder cancer markers were significantly higher in traditional tobacco users than in e-cigarette users. Systematic review registration : PROSPERO (CRD42023455600: https://www.crd.york.ac.uk/PROSPERO/)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Feng, Huang, Peng, Liang, Deng, Zhang, Li and Wu.)

The practical implementation of massive multi-user multi-input-multi-output (MU-MIMO) downlink communication systems power amplifiers that are energy efficient; otherwise, the power consumption of the base station (BS) will be prohibitive. Constant envelope (CE) precoding is gaining increasing interest for its capability to utilize low-cost, high-efficiency nonlinear radio frequency amplifiers. Our work focuses on the topic of CE precoding in massive MU-MIMO systems and presents an efficient CE precoding algorithm. This algorithm uses an alternating minimization (AltMin) framework to optimize the CE precoded signal and precoding factor, aiming to minimize the difference between the received signal and the transmit symbol. For the optimization of the CE precoded signal, we provide a powerful approach that integrates the majorization-minimization (MM) method and the fast iterative shrinkage-thresholding (FISTA) method. This algorithm combines the characteristics of the massive MU-MIMO channel with the second-order Taylor expansion to construct the surrogate function in the MM method, in which minimizing this surrogate function is the worst-case of the system. Specifically, we expand the suggested CE precoding algorithm to involve the discrete constant envelope (DCE) precoding case. In addition, we thoroughly examine the exact property, convergence, and computational complexity of the proposed algorithm. Simulation results demonstrate that the proposed CE precoding algorithm can achievean uncoded biterror rate (BER) performance gain of roughly 1dB compared to the existing CE precoding algorithm and has an acceptable computational complexity. This performance advantage also exists when it comes to DCE precoding.

Heterogeneity of pyrolytic parameters in municipal solid waste (MSW) significantly hinders its waste-to-energy efficiency. So far, hardly any light has been shed on current pyrolytic heterogeneity conditions or feasible pyrolytic homogeneity enhancement approaches of MSW. Accordingly, pyrolytic properties (E a and logA) of 130 MSW samples in 6 categories were collected from literature. A kinetic parameters clustering-based sorting strategy for MSW was proposed. A so-called C index was established to compare their sorting performance for E a and logA against two traditional sorting strategies (substance categorization and density clustering). Results showed that the proposed sorting strategies outperformed the traditional ones in pyrolytic homogeneity enhancement, where the optimal C&#95;E a and C&#95;logA reached 1578.30 kJ/mol and 93.11 -log min. Among investigated clustering methods, k-means clustering outperformed hierarchical clustering, which could be attributed to its adaptability to the sample structure. Future perspectives involving data set expansion, model framework development, and downstream technologies matching were also discussed. The index C established in this study can be used to evaluate other clustering models., 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.)

Objective: Acute visual impairment is the most feared complication of giant cell arteritis (GCA) but is challenging to predict. Magnetic resonance imaging (MRI) evaluates orbital pathology not visualized by an ophthalmologic examination. This study combined orbital and cranial vessel wall MRI to assess both orbital and cranial disease activity in patients with GCA, including patients without visual symptoms., Methods: Patients with suspected active GCA who underwent orbital and cranial vessel wall MRI were included. In 14 patients, repeat imaging over 12 months assessed sensitivity to change. Clinical diagnosis of ocular or nonocular GCA was determined by a rheumatologist and/or ophthalmologist. A radiologist masked to clinical data scored MRI enhancement of structures., Results: Sixty-four patients with suspected GCA were included: 25 (39%) received a clinical diagnosis of GCA, including 12 (19%) with ocular GCA. Orbital MRI enhancement was observed in 83% of patients with ocular GCA, 38% of patients with nonocular GCA, and 5% of patients with non-GCA. MRI had strong diagnostic performance for both any GCA and ocular GCA. Combining MRI with a funduscopic examination reached 100% sensitivity for ocular GCA. MRI enhancement significantly decreased after treatment (P < 0.01)., Conclusion: In GCA, MRI is a sensitive tool that comprehensively evaluates multiple cranial structures, including the orbits, which are the most concerning site of pathology. Orbital enhancement in patients without visual symptoms suggests that MRI may detect at-risk subclinical ocular disease in GCA. MRI scores decreased following treatment, suggesting scores reflect inflammation. Future studies are needed to determine if MRI can identify patients at low risk for blindness who may receive less glucocorticoid therapy., (© 2024 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Rationale and Objectives: To analyse the MRI-based radiomics and delta-radiomics features to establish radiomics models for predicting the radiographic progression of osteoarthritis (OA)., Materials and Methods: The data used in this research come from the dataset of the FNIH Biomarker Consortium Project within the Osteoarthritis Initiative (OAI). 565 participants randomly divided into training and validation groups at a 7:3 ratio. The training cohort consisted of 395 participants and included 202 cases. The validation cohort consisted of 170 participants and included 87 cases. Least absolute shrinkage and selection operator (LASSO) was used for feature selection. Support vector machine (SVM) was used to establish radiomics models and clinical and biomarker models for predicting the radiographic progression of OA. The predictive ability of the model was evaluated by the area under the curve (AUC)., Results: The baseline, 24 M, Delta, and two combination radiomics models (Baseline and Delta, 24 M and Delta) all showed good predictive performance in the training and validation cohorts, with the combination model exhibiting the best performance. In the training cohort, the AUCs were 0.851 (95% CI: 0.812-0.890), 0.825 (95% CI: 0.784-0.865), 0.804 (95% CI: 0.761-0.847), 0.892 (95% CI: 0.860-0.924) and 0.884 (95% CI: 0.851-0.917), respectively. The AUCs in the validation cohort were 0.741 (95% CI: 0.667-0.814), 0.786 (95% CI: 0.716-0.856), 0.745 (95% CI: 0.671-0.819), 0.781 (95% CI: 0.711-0.851) and 0.802 (95% CI: 0.736-0.869), respectively. As compared, the clinical and biomarker models have AUC < 0.74. The DeLong test showed that the predictive performance of the radiomics models in the training and validation cohorts was significantly better than that of the clinical and biomarker models (P < 0.001)., Conclusion: The MRI-based radiomics models of the patella all showed good predictive performance performed better than the clinical and biomarker models in predicting the radiographic progression of OA. Delta radiomics can improve the predictive performance of the single time model, the combined model of 24 M and Delta provided the best predictive performance., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest in this work., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Due to the radioactivity of uranium, the discharged nuclear wastewater not only causes certain damage to the ecology, but also causes certain harm to human life and health. Adsorption is considered to be one of the most effective ways to remove uranium. In this paper, a kind of MoS 2 adsorbent was prepared by the solid phase synthesis method and functionalized with NiCo-LDH. The raw materials of MoS 2 are cheap and easy to obtain, and the preparation conditions are simple, and large quantities can be obtained without limitations. MoS 2 functionalized with NiCo-LDH provides more adsorption sites for the adsorbent and at the same time improves the hydrophilicity of the adsorbent, so that the active sites can fully combine with uranyl ions. The maximum adsorption capacity of the Langmuir isothermal adsorption model is 492.83 mg g -1 . The selective adsorption capacity of uranium can reach 76.12% in the multi-ion coexistence system. By analyzing the adsorption mechanism with FT-IR and XRD, it is believed that on the one hand, UO 2 2+ forms a covalent bond with Mo in MoS 2 and coordinates with S on the surface of MoS 2 . On the other hand, UO 2 2+ enters the NiCo-LDH layer for ion exchange with NO 3 - and coordinates with -OH on the surface of NiCo-LDH. The successful preparation of the MoS 2 /NiCo-LDH composite provides a certain application prospect for the uranium adsorption field.

Background: Previous studies investigating the association between the geriatric nutrition risk index (GNRI) and sarcopenia either lacked longitudinal evidence or narrowly focused on specific populations., Aims: We aimed to reveal longitudinal associations of GNRI with sarcopenia risk in community-dwelling Chinese. We also investigated interaction effects of potential factors on such associations., Methods: We included participants aged ≥ 50 years with sufficient data from the WCHAT study who did not have sarcopenia at baseline and completed sarcopenia assessment during follow-up. GNRI was calculated according to the formula based on serum albumin, height and weight. Sarcopenia was diagnosed according to the 2019 AWGS consensus. Longitudinal associations between GNRI and sarcopenia were estimated by logistic regression with GNRI as either a continuous or categorical variable by tertiles, using generalized estimating equations (GEE) as sensitivity analyses. Subgroup analyses by potential covariates were conducted to detect interaction effects., Results: A total of 1907 participants without baseline sarcopenia were finally included, of whom 327 (17.1%) developed incident sarcopenia during 5-year follow-up. After controlling for confounders, sarcopenia risk decreased with each one standard deviation increase in GNRI (OR adjusted =0.36, 95% CI 0.31-0.43), and it also decreased successively from the lowest (< 111.2) through middle (111.2-117.7) to the highest (≥ 117.8) tertile of the GNRI level (P for trend < 0.001). Similar results were yielded by GEE. Such associations generally remained robust across subgroups with distinct characteristics, while significant differences were observed between different age groups (≥ 65 vs. <65 years) (interaction P-value < 0.05)., Conclusion: GNRI is longitudinally associated with sarcopenia risk with possibly age-specific differences in association magnitude, which holds implications for policymakers to conduct population-based risk assessment., (© 2024. The Author(s).)

Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the FlpIn™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS)., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pleckstrin homeolike domain, family A, member 1 (PHLDA1) is a multifunctional protein that plays diverse roles in A variety of biological processes, including cell death, and hence its altered expression has been found in different types of cancer. Although studies have shown a regulatory relationship between p53 and PHLDA1, the molecular mechanism is still unclear. Especially, the role of PHLDA1 in the process of apoptosis is still controversial. In this study, we found that the expression of PHLDA1 in human cervical cancer cell lines was correlated with the up-expression of p53 after treatment with apoptosis-inducing factors. Subsequently, the binding site and the binding effect of p53 on the promoter region of PHLDA1 were verified by our bioinformatics data analysis and luciferase reporter assay. Indeed, we used CRISPR-Cas9 to knockout the p53 gene in HeLa cells and further confirmed that p53 can bind to the promoter region of PHLDA1 gene, and then directly regulate the expression of PHLDA1 by recruiting P300 and CBP to change the acetylation and methylation levels in the promoter region. Finally, a series of gain-of-function experiments further confirmed that p53 re-expression in HeLa p53-/- cell can up-regulate the reduction of PHLDA1 caused by p53 knockout, and affect cell apoptosis and proliferation. Our study is the first to explore the regulatory mechanism of p53 on PHLDA1 by using the p53 gene knockout cell model, which further proves that PHLDA1 is a target-gene in p53-mediated apoptosis, and reveals the important role of PHLDA1 in cell fate determination., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Xylariomycetidae comprises extremely diverse taxa that are widespread on decaying wood worldwide. An investigation of the diversity of microfungi on oil tree plantations in Sichuan Province was conducted during 2020-2021. Twelve saprobic taxa representing five species were identified as members of Amphisphaeriales and Xylariales through morphological comparisons. Phylogenetic analyses of combined ITS, LSU, rpb2 , tub2 and tef1 sequence data indicated a distinct clade formed by three strains within Xylariomycetidae, unrelated to any currently recognized families. Thus, a novel anthostomella-like genus, Bicellulospora , is proposed and treated as Xylariales genera incertae sedis . Bicellulospora is characterized by dark brown to black, immersed, subglobose ascomata with a clypeus, cylindrical asci, and hyaline to yellowish brown, inequilaterally ellipsoidal ascospores with a large upper cell and a dwarf lower cell. Two new species of Amphisphaeria , namely A. oleae and A. verniciae , are introduced based on multi-gene phylogenetic analyses (ITS, LSU, rpb2 and tub2 ) coupled with morphological characteristics. Amphisphaeria micheliae and Endocalyx ptychospermatis are reported as new host records.

Mutations in a Plasmodium de-ubiquitinase UBP1 have been linked to antimalarial drug resistance. However, the UBP1-mediated drug-resistant mechanism remains unknown. Through drug selection, genetic mapping, allelic exchange, and functional characterization, here we show that simultaneous mutations of two amino acids (I1560N and P2874T) in the Plasmodium yoelii UBP1 can mediate high-level resistance to mefloquine, lumefantrine, and piperaquine. Mechanistically, the double mutations are shown to impair UBP1 cytoplasmic aggregation and de-ubiquitinating activity, leading to increased ubiquitination levels and altered protein localization, from the parasite digestive vacuole to the plasma membrane, of the P. yoelii multidrug resistance transporter 1 (MDR1). The MDR1 on the plasma membrane enhances the efflux of substrates/drugs out of the parasite cytoplasm to confer multidrug resistance, which can be reversed by inhibition of MDR1 transport. This study reveals a previously unknown drug-resistant mechanism mediated by UBP1 through altered MDR1 localization and substrate transport direction in a mouse model, providing a new malaria treatment strategy., (© 2024. The Author(s).)

Sterilization is essential for ready-to-eat foods; however, it tends to degrade the quality of the product. To explore the role of antioxidants in regulating the edible quality of roasted Pacific white shrimp after sterilization, color changes, degree of oxidation, microstructure and quality of roasted shrimp treated with tea polyphenols, phytic acid, rosemary extract, and d-sodium erythorbate were investigated. Tea polyphenol-treated roasted shrimp had the lowest Maillard intermediate products and browning strength after sterilization; phytic acid significantly reduced carbonyl content and TBARS value; rosemary extract exhibited the lowest level of free radicals, while d-sodium erythorbate preserved a relatively intact myofibrillar structure. Correlation analysis revealed a negative correlation between the degree of oxidation and the edible quality of roasted shrimp after sterilization. Therefore, the addition of antioxidants inhibited oxidation and improved the quality of roasted shrimp, and different antioxidants had diverse effects on the quality improvement of roasted shrimp after thermal sterilization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)