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Purpose: Breath-hold techniques are widely used in radiation therapy to minimize respiratory-induced tumor or organ-at-risk motion. However, residual motion persists, necessitating a reliable daily evaluation method., Methods: At our institution, fiducial markers serve as surrogates for target localization in pancreatic cancer treatment. We developed an automated method to detect fiducial markers in every projection image of cone-beam computed tomography (CBCT) scans acquired for patient setup and positioning verification. This method was retrospectively validated using data from nine pancreatic cancer patients., Results: Residual motion was observed in all patients during breath-hold maneuvers. Intrafraction target motion in repeated breath-hold simulation CT scans averaged 1.9 ± 2.2 mm, with a maximum displacement of 8 mm in the superior-inferior direction. Within a single CBCT scan, residual motion reached up to 7.3 mm, with an average drifting range of 3.8 ± 1.1 mm across 94 CBCT scans. The average standard deviation of drift was 1.5 ± 0.5 mm. Significant drift (1.3 ± 1.2 mm) and inter-breath-hold gaps (2.6 ± 2.0 mm) were detected within the same CBCT scan., Conclusion: Our method enables daily residual motion assessment without additional equipment or extra radiation exposure. This information is critical for refining planning margins in online adaptive radiation therapy, improving treatment precision and patient safety., (© 2025 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

A longed lack of control over harmful stimuli can lead to learned helplessness (LH), a significant factor in depression. However, the cellular and molecular mechanisms underlying LH, and eventually behavioral despair, remain largely unknown. The deleted in colorectal cancer (dcc) gene is associated with the risk of depression. However, the therapeutic potential and regulation mechanism of DCC in behavioral despair are still uncertain. In this study, we showed that depressive stimulators, including LH, lipopolysaccharide, and unpredictable chronic mild stress, triggered an elevation in DCC expression in the medial prefrontal cortex (mPFC). Additionally, elevated DCC expression in the mPFC was crucial in inducing behavioral despair, as evidenced by the induction of behavioral despair in normal mice and exacerbation of behavioral despair in LH mice upon DCC overexpression. By contrast, neutralizing DCC activity ameliorated LH-induced behavioral despair. Importantly, we elucidated that pathological DCC expression was attributable to the excessive excitation of CaMKII + neurons in a manner dependent on the calpain-mediated degradation of SCOP and aberrant phosphorylation of the ERK signaling pathway. In addition, the increase in DCC expression led to a decreased excitability threshold in CaMKII + neurons in the mPFC, which was supported by the observation that the ligand netrin 1 increased the frequency of action potential firing and of spontaneous excitatory postsynaptic currents in CaMKII + neurons. In conclusion, our data indicate that LH triggers the excessive excitation of CaMKII + neurons and activation of calpain-SCOP/ERK signaling to promote DCC expression, and DCC represents a crucial target for the treatment of LH-induced behavioral despair in male mice., Competing Interests: Ethics approval and consent to participate: All animal experiments in this study were complied with National Institutes of Health (NIH) guidelines for the Care and Use of Laboratory Animals and approved by the Animal Ethics Committee of Anhui University of Chinese Medicine (AHUCM-mouse-2022014). Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Nitrogen-rich materials have attracted considerable attention in recent years as potential high-energy-density materials (HEDMs). However, their metastability poses substantial challenges for synthesis under ambient conditions. Here, we employ a novel strategy to explore energetic and structural features of the nitrogen-rich BN n + ( n = 4-16) clusters by doping with the light non-metal boron. A series of boron-doped nitrogen clusters, with nitrogen content ranging from 83% to 96%, were obtained by laser ablation and analyzed via time-of-flight mass spectrometry. The results indicate that the BN 6 + cluster is dominant in the mass spectrum, while the BN 12 + cluster exhibits the highest abundance after cooling the cluster source with liquid nitrogen. To further confirm the experimental results, extensive structure searches for BN n + ( n = 4-16) clusters are conducted using the CALYPSO method and density functional theory (DFT) calculations. The calculations show that BN 6 + (singlet) exhibits a planar [B(NN) 3 ] + three-branched geometry with D 3h symmetry, while BN 12 + (singlet) adopts a [(linear-N 6 )B(N 3 ) 2 ] + branched geometry with C 1 symmetry. Stability analyses reveal the relatively high structural stabilities of BN 6 + and BN 12 + clusters and agree well with the experimental findings. Notably, the gas-phase enthalpy of formation of the BN 12 + cluster is remarkably high, -1385.10 kJ mol -1 , suggesting its potential as a high-energy building block for HEDM construction. The present findings enhance the structural diversities of non-metal-doped nitrogen clusters, and offer new perspectives for the rational design and synthesis of nitrogen-rich energetic materials.

A synergistic Pd/Cu catalyst system has been developed for stereodivergent transformation of Morita-Baylis-Hillman (MBH) carbonates and Schiff bases derived from simple amino acids to afford a series of optically active β-branched γ-methyleneglutamic acid derivatives with adjacent tertiary/tertiary and quaternary/tertiary stereocenters in high yields (up to 96 %) with excellent diastereo- and enantioselectivities (>20/1 dr and >99 % ee in most cases) under mild conditions. The use of SKP ligand is disclosed to be crucial for the success of the transformation, and in particular allowing the reaction to proceed at low catalyst loading (0.02 mol % for Pd and 0.08 mol % for Cu). The high efficiency of the catalysis was attributed to the formation of intimate ion pair complex A1, composed of Pd-phosphonium cation and a t-butoxide anion, which would facilitate the subsequent deprotonation and C-C coupling events. All four stereoisomers of the β-branched glutamic acid derivatives were readily prepared by permutation of the catalyst enantiomers. Synthetic utility of the methodology was exemplified by efficient synthesis of a fused pyrrolooxazolidinone with three contiguous chiral centers, highlighting the power of synergistic Pd/Cu catalysis for asymmetric allylic alkylation with MBH carbonates., (© 2024 Wiley-VCH GmbH.)

Ternary I-III-VI semiconductors are useful light-capture materials, but the presence of a special donor-acceptor pair complicates the dynamics of carriers in the photocatalytic process, and the combined effect of multiple types of defects makes it difficult to study the single type of defect on carrier dynamics. Here, excess inorganic S 2- ligand is used to passivate the surface defects of the nonstoichiometric ratio Ag-In-Zn-S quantum dots (QDs), which enables the systematic investigation of the effects of high-density donor-acceptor pairs on the carrier separation and transfer path during photocatalysis. The results show that the donor-acceptor pair defects in quantum dots can effectively separate the carriers because the defects generated by the donor or acceptor can effectively "store" the carriers at the fixed energy level and provide an additional path for the transfer of the carriers. The calculation results of density functional theory are consistent with the characterized structure of FTIR, proving the feasibility of inorganic S 2- replacing MPA. The indium vacancy (V In ) in ZIS nanosheets serves as a carrier stored in the donor-acceptor pairs, effectively optimizing the dynamics of the carrier. The h + in the donor-acceptor pair and the e - on V In attract each other through the built-in electric field and radiate energy in the form of visible light. Through this strategy, the photocatalytic hydrogen production efficiency of the heterojunction can reach up to 80.7 mmol·g -1 ·h -1 , which is more than 1400 times the overall hydrogen production efficiency of AgInZnS 3 and AgInS-ZnS. This work provides some theoretical guidance for the systematic study of the effects of the donor-acceptor pair on charge carrier dynamics.

Traditional protein engineering methods, such as directed evolution, while effective, are often slow and labor-intensive. Advances in machine learning and automated biofoundry present new opportunities for optimizing these processes. This study devises a protein language model-enabled automatic evolution platform, a closed-loop system for automated protein engineering within the Design-Build-Test-Learn cycle. The protein language model ESM-2 makes zero-shot prediction of 96 variants to initiate the cycle. The biofoundry constructs and evaluates these variants, and feeds the results back to a multi-layer perceptron to train a fitness predictor, which then makes prediction of second round of 96 variants with improved fitness. With the tRNA synthetase as a model enzyme, four-rounds of evolution carried out within 10 days lead to mutants with enzyme activity improved by up to 2.4-fold. Our system significantly enhances the speed and accuracy of protein evolution, driving faster advancements in protein engineering for industrial applications., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

A highly stable electrochemiluminescent (ECL) sensor based on graphitic carbon nitride (GCN)/Pb 2+ /polypyrrole (PPy) was developed to detect trace copper ions. The hydrochloric acid immersion technique was applied to rearrange PPy chains for the first time. Under optimal experimental conditions, the ECL intensity increased linearly with the increase of Cu 2+ concentration in solution from 10 -12 M to 10 -6 M (1 pM to 1 μM), with a super low limit of detection (LOD) of 10 -12 M (1 pM) (S/N = 3). Additionally, the impact of detection on the localized states of the composite nanomaterial was revealed by applying Vienna ab initio Simulation Package (VASP) and Gaussian 16.

Objective: Immune checkpoint inhibitors (ICIs) have demonstrated substantial efficacy in patients with advanced non-small cell lung cancer (NSCLC). However, the optimal duration of ICI therapy remains unclear, and limited real-world data are available. The aim of this study was to evaluate the relationship between ICI therapy duration and overall survival (OS) in patients who achieved varying best overall response (BOR) during ICI treatment, and to compare patients treated for 6 to 18 months vs. at least 18 months., Methods: This retrospective cohort study included adult patients diagnosed with advanced NSCLC who received ICI therapy at the Zhejiang Cancer Hospital between 2017 and 2022. Data collection ended on May 1, 2024, and statistical analysis was performed between May and June 2024., Results: Using strict entry criteria, we screened 487 patients with advanced NSCLC and identified 134 eligible patients. Among these patients, the median durations of immunotherapy and follow-up were 24.57 months and 43.60 months, respectively. The objective response rate (ORR) was 58.2%, and the median progression-free survival (PFS) was 10.6 months. Median OS was not reached. At the last follow-up, 54 patients had no disease progression, and 118 patients remained alive. Patients treated with ICI therapy for ≥ 18 months had superior survival to those treated for 6 to 18 months ( P = 0.039). Further analysis revealed that the survival benefit was associated with BOR during ICI therapy. Specifically, patients achieving complete response/partial response (CR/PR) who received ≥ 18 months of ICI therapy had a trend toward longer median OS than those treated for 6 to 18 months, but the difference did not reach statistical significance ( P = 0.177). Patients with stable disease (SD) who received ≥ 18 months of ICI therapy had a statistically longer median OS than those treated for 6 to 18 months ( P = 0.019). Among patients treated with ICIs for ≥ 18 months, 24 continued with ICI-based therapy and achieved a median PFS 2 of 6.67 months, an ORR of 33.3%, and a disease control rate (DCR) of 83.3%., Conclusions: This study provides real-world evidence and novel insights into the need for continuing ICI therapy beyond 18 months in patients with advanced NSCLC who do not exhibit progressive disease. For patients achieving SD during ICI therapy, a treatment duration of at least 18 months appears appropriate. For patients achieving CR/PR, treatment decisions should be individualized according to patient-specific circumstances. However, owing to the retrospective study design, potential selection bias and confounding factors might have influenced the results. Therefore, our findings require further validation in prospective clinical studies., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2025 The Authors.)

Purpose: Emerging evidences have indicated a role of the complement system in the pathogenesis of diabetic nephropathy (DN). Thus, this study was conducted to explore the complement system-related key biomarkers for patients with DN., Methods: DN microarray datasets were downloaded from the GEO database, followed by differentially expressed genes (DEGs) screening. Complement system-related genes (CSRGs) were searched from various databases. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to screen the DN-related genes, then the differential CSRGs (DCSRGs) were identified, followed by protein-protein interaction (PPI) network construction. In addition, key biomarkers were acquired by two machine learning algorithms, then immune infiltration analysis, Gene Set Enrichment Analysis (GSEA), and potential drugs screening were conducted. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting were utilized to detect the ITGB2 expression. Then the cell viability, inflammatory factors, and the expression of epithelial-mesenchymal transition (EMT) and fibrosis markers were determined by using Cell Counting Kit-8 (CCK-8) assay, enzyme linked immunosorbent assay (ELISA), western blotting assays, respectively., Results: In total, 1012 DEGs and 974 DN-related genes were screened, and intersection analysis of the three (DN-related genes, DEGs and CSRGs) yielded 13 intersection genes, which were considered as the DCSRGs. Subsequently, 2 key biomarkers were identified by machine learning, namely VWF and ITGB2. The VWF and ITGB2 were both enriched in the pathways of chemokine signaling pathway, CAMs, focal adhesion and natural killer cell-mediated cytotoxicity, and significantly correlated with the activated mast cells, resting NK cells, and macrophages. Also, VWF and ITGB2 were significantly related to the clinical features, including age, serum creatinine level, and GFR (MDRD). Besides, mRNA and protein expression levels of ITGB2 in HG-treated HK-2 cells were remarkably elevated. Moreover, the viability of HK-2 cells, expression of TNF-α, IL-6, IL-12, α-SMA, E-cadherin and vimentin in HK-2 cells changed by HG administration were reversed by ITGB2-silence., Conclusion: Complement system-related gene ITGB2 was overexpressed in DN, and inhibition of ITGB2 attenuated EMT and inflammation in DN., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Non-invasive prenatal testing is widely used for screening common fetal aneuploidy disorders such as trisomy 21, trisomy 18, and trisomy 13. However, its ability to detect rare autosomal trisomies has introduced a new layer of complexity and clinical uncertainty., Methods: A retrospective analysis was conducted on the prenatal diagnostic results and pregnancy outcomes of cases identified as high-risk for rare autosomal trisomies through non-invasive prenatal testing at the reproductive medicine center, Renmin hospital, Hubei university of medicine, from 2015 to 2023., Results: 66 cases identified as high-risk for rare autosomeal trisomies, yielding a detection rate of 0.20% (66/33,079). 7 declined amniocentesis, while the others underwent the procedure. Prenatal diagnostic procedures did not confirm the presence of the corresponding rare autosomal trisomy in any of these cases. Among the 66 cases of rare autosomal trisomies (RATs), 5 cases were lost to follow-up, and 1 case underwent termination of pregnancy (TOP) for personal reasons, leaving 60 cases with valid pregnancy outcomes. Of these 60 valid outcomes, 50 (83.33%) resulted in full-term births, while 10 (16.67%) experienced adverse pregnancy outcomes., Conclusion: Prenatal diagnosis for high-risk rare autosomal trisomies typically reveals a normal karyotype with no detectable chromosomal abnormalities, and most cases can achieve full-term pregnancy outcomes. However, adverse pregnancy outcomes such as preterm birth, fetal demise, placental abnormalities, and intrauterine growth restriction are common and should be given clinical attention and consideration., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Ethical Committee of Renmin Hospital, Hubei University of Medicine. Informed consent was provided by all patients or by the parents of the patients. The patients were informed of the diagnostic tests and genetic analysis before operations in accordance with the Declaration of Helsinki. Written informed consents to participate were obtained from participants. All methods were carried out in accordance with relevant guidelines and regulations. This study was carried out in compliance with the ARRIVE guidelines. Consent for publication: NA. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: The aim of this study was to describe the characteristics of exercise therapies in randomised controlled trials (RCTs) targeted at improving cognitive function and to assess their efficacy in COPD., Methods: We conducted a comprehensive search of eight databases, namely PubMed, Web of Science, Embase, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang and Weipu, covering the period from database construction to 23 April 2024. Our search specifically targeted RCTs studying the effects of exercise on cognitive functioning in COPD patients. Trials consisted of one or more exercise training interventions along with at least one cognitive outcome study. Two reviewers independently reviewed papers, extracted data and evaluated the research literature's quality using the Cochrane risk-of-bias assessment tool RoB 2.0 and the modified Jadad scale. Meta-analysis of Montreal Cognitive Assessment (MoCA) scores in the groups with and without exercise intervention was performed and subgroup analyses were undertaken to identify potential causes of heterogeneity., Results: We included a total of nine studies that included 578 COPD patients (69% male). Each study demonstrated that patients improved significantly in at least one cognitive component following training. All current research focuses on attention, executive function, motor ability, mental capacity, verbal fluency, visuoconstructive abilities and memory. The results revealed that exercise significantly improved MoCA scores in COPD patients (standardised mean difference (SMD) 0.576 (95% CI 0.054-1.097); p=0.029). A subgroup analysis of the duration of each intervention revealed that exercise training with an intervention duration of >30 min significantly improved overall cognitive performance in COPD patients (SMD 0.499 (95% CI -0.165-1.163); p=0.000, I 2 =0.0%). A subgroup analysis of varied intervention durations revealed that 4 weeks of exercise training significantly improved overall cognitive performance in COPD patients (SMD 0.202 (95% CI -0.238-0.641); p=0.000, I 2 =0.0%). In addition, just one study had a year-long follow-up period., Conclusion: Participation in exercise training, whether aerobic exercise alone or in combination with resistance or muscular strength, healthy qigong, dance or breathing exercises, can improve cognitive performance to varying degrees in people with COPD. Nonetheless, the findings should be regarded with caution due to the limitations of the included studies., Competing Interests: Conflict of interest: The authors declare that the study was conducted in the absence of any business or financial relationships that could be interpreted as potential conflicts of interest., (Copyright ©The authors 2025.)

Purpose: To compare clinical outcomes of eyes undergoing Descemet stripping automated endothelial keratoplasty (DSAEK) with 51-99 μm and <50 μm lenticules., Methods: Retrospective, multi-center case series of 480 eyes undergoing DSAEK with precut tissue from a single eye bank between 2019 and 2022 performed by five surgeons at five centers. Eyes were divided into 51-99 μm or <50 μm groups according to post-cut graft thickness. The main outcome measure was inter-group comparison according to best-corrected distance visual acuity (BCDVA); additional outcome measures were primary graft failure (PGF), rebubbling, and cystoid macular edema (CME) rates in context of specific preoperative risk factors, intraoperative characteristics, and vision-limiting vs. non-vision-limiting morbidities., Results: BCDVA at one year postoperatively was 0.5 ± 0.5 and 0.4 ± 0.4 logMAR for the 51-99 μm and <50 μm groups, respectively ( p  = 0.692). Regraft rate was 3.21% for 51-99 μm and 1.89% for <50 μm grafts ( p  = 0.4854). Rebubbling rate was 8.56% for the 51-99 μm group and 13.21% for the <50 μm group ( p  = 0.151). Analysis of rebubbled eyes showed no difference in rate of sulfur hexafluoride tamponade ( p  = 0.201), lenticule insertion method ( p  = 0.293), and glaucoma surgery history ( p  = 0.996). Higher rebubbling rates occurred in eyes with previous scleral-fixated intraocular lenses ( p  < 0.001). The effect of potential preoperative and intraoperative risk factors (e.g. insertion method ( p  = 0.979) and concurrent cataract surgery ( p  = 0.701)) on rebubbling was not significantly different between the two groups. CME rate was 4.01% for 51-99 μm and 7.54% for <50 μm groups ( p  = 0.131)., Conclusions: 51-99 μm and <50 μm DSAEK grafts offer similar visual outcomes. Both lenticule thicknesses have similar regrafting, rebubbling, and CME rates.

In hierarchical reinforcement learning, unsupervised skill discovery holds promise for overcoming the challenge of sparse rewards commonly encountered in traditional reinforcement learning. Although previous unsupervised skill discovery methods excelled at maximizing intrinsic rewards, they often overly prioritized skill diversity. Unrestrained pursuit of diversity leads skills to concentrate attention on unexplored domains, overlooking the internal consistency of skills themselves, resulting in the state visit distribution of individual skills lacking concentration. To address this problem, the Constrained Skill Discovery (CoSD) algorithm is proposed to balance the diversity and behavioral consistency of skills. CoSD integrates both the forward and the reverse decomposition forms of mutual information and uses the maximum entropy policy to maximize the information-theoretic objective of skill learning while requiring that each skill maintain low state entropy internally, which enhances the behavioral consistency of the skills while pursuing the diversity of the skills and ensures that the learned skills have a high degree of stability. Experimental results demonstrated that, compared with other skill discovery methods based on mutual information, skills from CoSD exhibited a more concentrated state visit distribution, indicating higher behavioral consistency and stability. In some complex downstream tasks, the skills with higher behavioral consistency exhibit superior performance., 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.)

Chitosan is an ideal coating film for food preservation, but the performance of a single chitosan coating film is not good. Herein, the liposome was prepared by embedding copper nanoparticles (CuNPs) and thyme essential oil (TEO) in the hydrophilic and hydrophobic double-domain structure formed by phospholipids, and combining with chitosan to obtain a chitosan-based coating film for litchi preservation. The liposome was well-dispersed and stable with an average particle size of about 190 nm. The liposome showed excellent controllable release properties, and the cumulative release rate of TEO was 65.17 % and that of CuNPs was 15.17 % after 7 days. Furthermore, the oxygen and water vapor barrier properties of the coating film were greatly improved. Importantly, the film possessed effective antioxidant, antibacterial activity and excellent safety, which presents a better fresh-keeping effect on litchi. This study provides insights into the design and manufacture of food packaging for controllable and long-lasting preservation., 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.)

Introduction: This study examines the usability and comfort of a behind-the-ear seizure detection device called brain seizure detection (BrainSD) that captures ictal electroencephalogram (EEG) data using four scalp electrodes., Methods: This is a feasibility study. Thirty-two patients admitted to a level 4 Epilepsy Monitoring Unit were enrolled. The subjects wore BrainSD and the standard 21-channel video-EEG simultaneously. Epileptologists analyzed the EEG signals collected by BrainSD and validated it using video-EEG data to confirm its accuracy. A poststudy survey was completed by each participant to evaluate the comfort and usability of the device. In addition, a focus group of UT Southwestern epileptologists was held to discuss the features they would like to see in a home EEG-based seizure detection device such as BrainSD., Results: In total, BrainSD captured 11 of the 14 seizures that occurred while the device was being worn. All 11 seizures captured on BrainSD had focal onset, with three becoming bilateral tonic-clonic and one seizure being of subclinical status. The device was worn for an average of 41 hours. The poststudy survey showed that most users found the device comfortable, easy-to-use, and stated they would be interested in using BrainSD. Epileptologists in the focus group expressed a similar interest in BrainSD., Conclusions: Brain seizure detection is able to detect EEG signals using four behind-the-ear electrodes. Its comfort, ease-of-use, and ability to detect numerous types of seizures make BrainSD an acceptable at-home EEG detection device from both the patient and provider perspective., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 by the American Clinical Neurophysiology Society.)

While fibroblast growth factor receptor 2 (FGFR2) emerges as an appealing cancer therapeutic target, so far there is no selective FGFR2 inhibitor on the market. Here, we report the discovery of a series of new selective, irreversible FGFR2 inhibitors with compound BW710 being the representative. Compound BW710 potently inhibited the proliferation of BaF3-FGFR2 cells with an IC 50 value of 2.8 nM, and was much less active against BaF3-FGFR1 and parental BaF3 cells with IC 50 values of >1000 nM. Kinase selectivity profiling revealed that BW710 completely abolished FGFR2 enzymatic activity and was selective against other 75 tyrosine kinases including FGFR1, FGFR3, and FGFR4 at 1 μM. The covalent binding mode between BW710 and FGFR2 was confirmed by MS spectrometry. Further evaluation showed that BW710 potently suppressed the FGFR2 signaling and selectively inhibited FGFR2-driven cancer cell proliferation. Additionally, BW710 also displayed reasonable pharmacokinetic properties with an oral bioavailability of 29 % in mice. Taken together, this study provides a potent, selective and orally bioavailable FGFR2 inhibitor for further development of FGFR2-targeted therapeutic agents., 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 © 2025 Elsevier Masson SAS. All rights reserved.)

Electric field-assisted aerobic composting (EAC) is a novel strategy for effectively mitigating nitrous oxide (N 2 O) emissions, but its deeper effects require further exploration. In this study, the differences in N 2 O emissions between the anode regions (AR) and cathode regions (CR) during EAC were evaluated. The cumulative N 2 O emission from the compost in CR was 32.77% lower than in AR. Compared to AR, the physicochemical properties of CR contribute to the reduction of N 2 O emission. PLS-PM analysis suggested that differences in N 2 O emission are primarily regulated by N-cycling related functional genes and N-containing substances, with different regulatory effects. In AR, functional genes and N-containing substances are significantly positively correlated with N 2 O emissions, whereas in CR, they are significantly negatively correlated. This study highlights the differences and effects of electrode regions in EAC on N 2 O emissions, offering new perspectives for future optimization., 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.)

Glioblastoma (GBM) remains a daunting oncological challenge because of its aggressive nature and resistance to conventional therapies. Inhibition of the intrinsic STING pathway in GBM hampers the effectiveness of immunotherapies. To overcome this clinical limitation, a Sequential Release HydroLipo System (SRHLS) is developed, in which hydrogels and nanoparticles are combined for controlled drug release. The SRHLS sequentially released decitabine and STING agonists, thereby correcting STING signaling dysfunction through epigenetic reprogramming and enhancing antitumor immunity. According to in vitro and in vivo experiments, the SRHLS reshaped the tumor microenvironment and markedly inhibited tumor growth, recurrence, and metastasis. These findings underscore the potential of the SRHLS as a promising therapeutic strategy for GBM., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The notorious tumor microenvironment (TME) usually becomes more deteriorative during phototherapeutic progress that hampers the antitumor efficacy. To overcome this issue, we herein report the ameliorative and adaptive nanoparticles (TPASIC-PFH@PLGA NPs) that simultaneously reverse hypoxia TME and switch photoactivities from photothermal-dominated state to photodynamic-dominated state to maximize phototherapeutic effect. TPASIC-PFH@PLGA NPs are designed by incorporating oxygen-rich liquid perfluorohexane (PFH) into the intraparticle microenvironment to regulate the intramolecular motions of AIE photosensitizer TPASIC. TPASIC exhibits a unique aggregation-enhanced reactive oxygen species (ROS) generation feature. PFH incorporation affords TPASIC the initially dispersed state, thus promoting active intramolecular motions and photothermal conversion efficiency. While PFH volatilization leads to nanoparticle collapse and the formation of tight TPASIC aggregates with largely enhanced ROS generation efficiency. As a consequence, PFH incorporation not only currently promotes both photothermal and photodynamic efficacies of TPASIC and increases the intratumoral oxygen level, but also enables the smart photothermal-to-photodynamic switch to maximize the phototherapeutic performance. The integration of PFH and AIE photosensitizer eventually delivers more excellent antitumor effect over conventional phototherapeutic agents with fixed photothermal and photodynamic efficacies. This study proposes a new nanoengineering strategy to ameliorate TME and adapt the treatment modality to fit the changed TME for advanced antitumor applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The instability of citral greatly limits its application in food field. This study aimed to develop a safe and green emulsifier-stabilized nanoemulsion (NE) to encapsulate citral for exerting its activities. A series of NEs were prepared using varying proportions (1:2 and 1:3) of sulfonated cellulose nanocrystalline- (CNC-C) and pea protein isolate- (PPI) mixture as emulsifier to encapsulate citral with different content (1 %, 2 %, and 3 %), and their stability, antioxidant and antibacterial activities were evaluated to identify the optimal system. When CNC-C and PPI proportion was 1:3 and citral content was 2 % (CC1-P3-C2), the obtained CC1-P3-C2 incorporated into pectin achieved the excellent preservation effect on kiwifruits and blueberries. It was attributed to the stability and functional activities of CC1-P3-C2. On the one hand, after storage (25 d) or at pH 11 or 100 mM NaCl, its size and polydispersity index were still within acceptance level (<300 nm and 0.3). On the other hand, it showed good antioxidant and antibacterial activities against Escherichia coli, Staphylococcus aureus, Botrytis cinerea, and Botryosphaeria dothidea, which was due to its high encapsulation efficiency (96.78 %). Therefore, CC1-P3-C2 showed a great application potential in fruit preservation, which also provided a feasible strategy to design stable citral NEs., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The fluctuations in emotions during constant help are unexplained by traditional emotion theories but may align with the predictive coding theory. This theory suggests that individuals tend to form expectations of others' help during social interactions. When outcomes exceed expectations, positive prediction errors are generated, potentially increasing gratitude. Conversely, constant help may build up expectations that surpass outcomes, resulting in negative prediction errors and reduced gratitude. Nevertheless, there is a lack of studies to examine the relationship between prediction errors and gratitude and its underlying mechanism. Here, we conducted two studies. Study 1 consistently found that higher expectations were associated with lower gratitude, when benefactors refused to help, in both reward-gaining and punishment-avoiding tasks. Moreover, prediction errors were positively and reliably linked to gratitude. Study 2 further identified that gratitude dynamically changed through an expectation-updating mechanism. A computational model incorporating predictive coding outperformed traditional theories in predicting the dynamics of gratitude. The findings support predictive coding theory, providing a temporal perspective and a mechanistic understanding of the fluctuations in gratitude, thus having implications for new interventions to improve mental health and well-being. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Ethnopharmacological Relevance: Positive deficiency and cancer toxicity are the main pathogenesis of colorectal cancer (CRC) lung metastasis. Yanghe decoction (YHD), a traditional Chinese medicine, has the effects of warming yang, tonifying blood, dispersing cold and clearing stagnation, adopting a treatment method that combines supporting the right and dispelling the wrong, which has remarkable efficacy in anti-tumor.Although, its precise mechanism of inhibiting the metastasis of colorectal cancer to the lung is still poorly understood., Aim of the Study: This study aimed to elucidate the antitumor properties of YHD within the context of colorectal cancer lung metastasis., Materials and Methods: Ultrahigh-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) was utilized to analyze the chemical composition of YHD. The anticancer activity of YHD was evaluated in a CRC lung metastasis mouse model by quantifying pulmonary metastatic nodules. The effects of YHD on CRC cell proliferation, apoptosis, cell cycle progression, and invasion were assessed using CCK-8 assays, flow cytometry, and Transwell assays. YHD-mediated immune modulation in tumor-bearing mice was evaluated by analyzing antitumor immunity, immunosuppressive cells, and cytokines in peripheral blood and tumor tissue. Gut microbiota analysis was conducted to determine the impact of YHD on the gut microbiota in mice., Results: Our analysis identified 1801 chemical markers in YHD. CFA exacerbated lung metastasis in CRC, whereas oral administration of YHD significantly mitigated this effect, as evidenced by the reduced number of metastatic lung nodules in CRC tumor-bearing mice. In vitro experiments demonstrated that YHD inhibits CRC cell proliferation, induces apoptosis, and suppresses invasion. In the lung tissues of mice with CRC metastasis treated with CFA, there was a significant reduction in NK cells and IL-21, along with an increase in M2 macrophages and IL-6. Following YHD treatment, there was a notable increase in NK cells and IL-21, accompanied by a decrease in M2 macrophages and IL-6 in lung tissues. YHD administration was also associated with an increase in beneficial bacterial species such as Bacillus and a decrease in deleterious bacterial species such as Oscillibacter., Conclusion: Our findings demonstrate that YHD inhibits lung metastasis in CRC by suppressing CRC cell proliferation and invasion, in addition to modulating the tumor microenvironment to favor antitumor immunity. These results provide a scientific basis for the clinical application of YHD in the treatment of CRC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Lung ultrasonography (LUS) is increasingly used to assess pulmonary diseases due to its safety and convenience. This study aimed to find out the association between the LUS score and the PaO 2 /FiO 2 ratio in neonatal pneumonia., Methods: This study prospectively enrolled 57 neonates with suspected pneumonia. LUS score (range 0-48) was evaluated by assessing 12 lung regions. The PaO 2 /FiO 2 ratio was calculated by dividing the arterial oxygen partial pressure by the fraction of inspired oxygen from blood gas analysis. Correlations were analyzed using Pearson's correlation coefficient., Results: Birth weight ranged 1 100-4 500 g (median 2 925 g), gestational age 27-41 weeks (median 37 weeks), and age 1-28 days (median 1 day). The LUS score was significantly correlated with the PaO 2 /FiO 2 ratio (r = 0.758, p < 0.001), arterial oxygen partial pressure (r = 0.731, p < 0.001), partial pressure of carbon dioxide (r = 0.213, p < 0.001), and oxygen saturation (r = 0.196, p < 0.001)., Conclusions: Our study demonstrates significant correlations between the LUS score and blood gas analysis indices in neonatal pneumonia., (© 2025 Wiley Periodicals LLC.)

Objective: To examine the relationship between body mass index (BMI), newly developed sleep disorders and functional outcome after moderate-to-severe traumatic brain injury (msTBI)., Methods: Retrospective data from the TBI Model Systems National Database was analyzed, focusing on the independent association between BMI, sleep disorder diagnosis, and functional outcome as measured by the Extended Glasgow Outcome Scale (GOSE) at 1-year post-injury. Linear and logistic regression were used., Results: Out of 2,142 participants, 84% reported no sleep disorder (NSD), 9% reported a sleep disorder before TBI (PreSD), and 7% developed a sleep disorder after TBI (PostSD). Over 50% of participants were overweight or obese. After adjusting for demographic and clinical characteristics, a one-unit increase of BMI at the time of rehabilitation admission was associated with 3.7% higher odds of PostSD (OR [95%CI]: 1.037 [1.007, 1.068], p  = 0.015). PostSD was associated with a 53.6% higher chance of unfavorable GOSE compared to NSD (OR [95%CI]: 1.536 [1.069-2.207], p  = 0.02) and an 81.7% higher chance compared to PreSD (OR [95% CI]: 1.817 [1.137-2.905], p  = 0.01)., Conclusion: Being overweight/obese and developing a sleep disorder had adverse effects on functional outcome, emphasizing the importance of addressing sleep and lifestyle factors in post-msTBI rehabilitation.

Numerous studies have shown that topical timolol is effective in treating infantile hemangioma (IH) with minimal adverse events. However, consensus is lacking on optimal timing, dosage, frequency, and safety parameters for this treatment. This study aims to explore the timing and safety of topical timolol treatment for superficial IH. A retrospective analysis included pediatric IH patients who underwent topical timolol treatment at the Department of Pediatric Surgery of Sichuan Provincial People's Hospital between January 2019 and January 2023. Medical records were reviewed for patient information, lesion characteristics, outcomes, and complications. Topical timolol was administered to 666 IH patients. Median follow-up was 10 months. 480 cases had excellent or good outcomes, while 186 had fair or poor outcomes. Patients ≤ 3 months had better outcomes than those > 3 months (Z = 4.713, P < 0.001). Small IH had better outcomes than large IH (Z = 1.991, P = 0.046). Lesion locations did not significantly affect outcomes (H = 10.252, P = 0.114). Respiratory problems occurred in 58 (8.7%) cases, localized skin irritation occurred in 48 (7.2%) cases, sleep disturbance occurred in 30 (4.5%) cases, and residual skin lesions occurred in 26 (3.9%) cases. In 59 (8.8%) cases the IH had relapses., Conclusions: Topical timolol is safe and effective for IH. Patients who are aged 1 < months ≤ 3 or have small (1.5 cm < max diameter ≤ 5 cm) IH are more likely to experience better outcomes. It also may reduce the incidence of residual skin lesions and relapse. Therefore it may be a useful alternative therapy option for superficial IH., What Is Known: • β-blockers are now considered to be first-line treatment of infantile hemangioma. • Topical timolol treatment is safe and effective for infantile hemangioma., What Is New: • Patients who are aged ≤ 3 months or have a max diameter ≤ 5 cm infantile hemangioma are likely to experience better outcomes by topical timolol treatment. • Topical timolol treatment may reduce the incidence of residual skin lesions and infantile hemangioma relapses., Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China (NO. 2024–48). Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: This study examined the association of e-cigarette use status and history of depression among American Indian (AI) adults who smoke., Method: We conducted a secondary data analysis using survey data from 375 AI adult smokers collected in 2016 at a tribally operated healthcare facility in northeast Oklahoma. Multivariable logistic regression was used to estimate the association between e-cigarette use and self-reported history of depression while adjusting for potential confounders., Results: In the adjusted analyses, compared to never users, current and former e-cigarette users had higher estimated odds of depression history (adj. OR 2.66; 95% CI 1.25-5.72 and adj. OR 2.38; 95% CI 1.36-4.26, respectively). Additional factors independently associated with a history of depression included having strong cravings to smoke (adj. OR 2.28; 95% CI 1.13-4.88) and having a history of chronic disease (adj. OR 2.09; 95% CI 1.20-3.70) after controlling for confounding variables., Conclusions: E-cigarette use among AI adult smokers was independently associated with a history of depression. Whether e-cigarette use among people who smoke results from depression or whether depression results from the combined use of e-cigarettes and cigarettes requires future research using a prospective cohort design., Competing Interests: Declarations. Ethics Approval: The Cherokee Nation and the University of Oklahoma Health Sciences Institutional Review Boards approved this project. Consent to Participate: This was a secondary data analysis of a de-identified dataset. Therefore, informed consent was unnecessary. However, all participants consented during primary data collection. Competing Interests: The authors declare no competing interests., (© 2025. W. Montague Cobb-NMA Health Institute.)

The hepatoprotective effect of the fruit of Lycium barbarum has been documented in China over millennia. Lycium barbarum polysaccharides (LBPs) were the first macromolecules reported to mitigate liver fibrosis in carbon tetrachloride (CCl 4 )-treated mice. Herein, a neutral peptidoglycan, named as LBPW, was extracted from the fruit of Lycium barbarum. In this study, we investigated the hepatoprotective mechanisms of LBPW. CCl 4 -induced liver fibrosis mice were administered LBPW (50, 100, 200 mg ·kg -1  ·d -1 , i.p.) or (100, 200, 300 mg· kg -1  ·d -1 , i.g.) for 6 weeks. We showed that either i.p. or i.g. administration of LBPW dose-dependently attenuated liver damage and fibrosis in CCl 4 -treated mice. Pharmacokinetic analysis showed that cyanine 5.5 amine (Cy5.5)-labeled LBPW (Cy5.5-LBPW) could be detected in the liver through i.p. and i.g. administration with i.g.-administered Cy5.5-LBPW mainly accumulating in the intestine. In TGF-β1-stimulated LX-2 cells as well as in the liver of CCl 4 -treated mice, we demonstrated that LBPW significantly upregulated Smad7, a negative regulator of TGF-β/Smad signaling, to retard the activation of hepatic stellate cells (HSCs) and prevent liver fibrosis. On the other hand, LBPW significantly boosted the abundance of Akkermansia muciniphila (A. muciniphila) and fortified gut barrier function. We demonstrated that A. muciniphila might be responsible for the efficacy of LBPW since decreasing the abundance of this bacterium by antibiotics (Abs) blocked the effectiveness of LBPW. Overall, our results show that LBPW may exert the hepatoprotective effect via rebalancing TGF-β/Smad7 signaling and propagating gut commensal A. muciniphila, suggesting that LBPW could be leading components to be developed as new drug candidates or nutraceuticals against liver fibrosis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Liver fibrosis, mainly arising from chronic viral or metabolic liver diseases, is a significant global health concern. There is currently only one FDA-approved drug (Resmetirom) in the market to combat liver fibrosis. Both galectin-3 and epidermal growth factor receptor (EGFR) play important roles in liver fibrosis, while galectin-3 may interact with EGFR. Galectin-3 inhibitors, typically lactose or galactose derivatives may inhibit liver fibrosis. We hypothesized that targeting both galectin-3 and EGFR may have better effect against liver fibrosis. Here, EGFR inhibitor erlotinib was used in a series of designed galectin-3 inhibitors after hybridization with the pharmacophore structure in reported galectin-3 inhibitors to impede hepatic stellate cells (HSCs) activation by a typical method of click chemistry. Bioactivity test results showed that compound 29 suppressed TGF-β-induced upregulation of fibrotic markers (α-SMA, fibronectin-1, and collagen I). The preferred compound 29 displayed better binding to galectin-3 (K D =52.29 μM) and EGFR protein (K D =3.31 μM) by SPR assay. Further docking studies were performed to clarify the possible binding mode of compound 29 with galectin-3 and EGFR. Taken together, these results suggested that compound 29 could be a potential dual galectin-3 and EGFR inhibitor as leading compound for anti-liver fibrosis new drug development., (© 2024 Wiley-VCH GmbH.)

The flower of Gomphrena globosa (G. globosa.) is used as Chinese traditional medicine and functional food. Extractions from G. globosa. have been reported to exert hepatoprotective effects. We further hypothesized that the polysaccharide components, as a bioactive ingredient, might have anti-fatty and hepatitis function. Here, a novel homogeneous arabinoglucan GGL0.05S1 (Mw = 83.9 kDa) from this flower, was characterized by monosaccharide composition analysis, methylation analysis, and NMR. Structural analysis showed that the backbone of GGL0.05S1 consists of →4)-α-Glcp-(1→ and →4,6)-α-Glcp-(1→ residues, and the branched chain linked to the main chain via C-6 of →4,6)-α-Glcp-(1→ in the form α-Araf-(1→[4)-α-Glcp-(1] b → (b > 2). In vitro experiments demonstrated that GGL0.05S1 could inhibit lipid deposition and ROS overload in free fatty acid-induced hepatocytes, meanwhile in vivo tests showed that GGL0.05S1 effectively protected against liver injury, steatohepatitis, and fibrosis in a CDA-HFD-fed MASH model. Mechanism study further uncovered that GGL0.05S1 augmented the expression and antioxidant ability of thioredoxin protein that ameliorated oxidative stress, promoted fatty acid β-oxidation and mitophagy, up to reducing lipotoxicity and alleviating inflammation via inhibiting NLRP3 signaling pathway. Overall, GGL0.05S1 might be a potential novel active compound with liver-protective effect from G. globosa., and which is informative for anti-MASH new drug development., 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.)

An optimized multi-stage separation strategy was developed to purify lily bulb polyphenol oxidase (PPO) for revealing its molecular structure. The PPO was purified 14.64-fold with high specific activity of 153,900 U/mg via optimized conditions of phosphate buffer pH (6.5), solid-liquid ratio (1:3), PVPP content (2 %), extraction time (4 h), followed by 30 %-50 % ammonium sulfate, diethylaminoethyl ion-exchange chromatography (0.1 M NaCl), and size exclusion chromatography. The PPO was identified as a dimeric protein with molecular weight of 135 kDa, containing 58.79 % random coil, 20.78 % α-helix, 17.41 % β-folding, and 3.02 % β-corner. The three-dimensional structure via homology modeling suggested that active center CuA bound to His151, His172, and His181, CuB bound to His307, His311, and His341. Furthermore, molecular docking indicated that its Phe337 and Tyr312 residues were catalytic cavity gates of catechol and 4-methylcatechol, respectively. Therefore, this study successfully analyzed purified PPO structure and further provided a theoretical foundation for its browning mechanism., Competing Interests: Declaration of competing interest No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors for publication. The work described was original research that has not been published previously, and not under consideration for publication elsewhere. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Microvascular invasion (MVI) is a significant risk factor for recurrence and metastasis following hepatocellular carcinoma (HCC) surgery. Currently, there is a paucity of preoperative evaluation approaches for MVI., Aim: To investigate the predictive value of texture features and radiological signs based on multiparametric magnetic resonance imaging in the non-invasive preoperative prediction of MVI in HCC., Methods: Clinical data from 97 HCC patients were retrospectively collected from January 2019 to July 2022 at our hospital. Patients were classified into two groups: MVI-positive ( n = 57) and MVI-negative ( n = 40), based on postoperative pathological results. The correlation between relevant radiological signs and MVI status was analyzed. MaZda4.6 software and the mutual information method were employed to identify the top 10 dominant texture features, which were combined with radiological signs to construct artificial neural network (ANN) models for MVI prediction. The predictive performance of the ANN models was evaluated using area under the curve, sensitivity, and specificity. ANN models with relatively high predictive performance were screened using the DeLong test, and the regression model of multilayer feedforward ANN with backpropagation and error backpropagation learning method was used to evaluate the models' stability., Results: The absence of a pseudocapsule, an incomplete pseudocapsule, and the presence of tumor blood vessels were identified as independent predictors of HCC MVI. The ANN model constructed using the dominant features of the combined group (pseudocapsule status + tumor blood vessels + arterial phase + venous phase) demonstrated the best predictive performance for MVI status and was found to be automated, highly operable, and very stable., Conclusion: The ANN model constructed using the dominant features of the combined group can be recommended as a non-invasive method for preoperative prediction of HCC MVI status., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

Liver fibrosis may lead to cirrhosis and even cancer without effective clinical medicine available. Previous studies demonstrated that galactan-containing pectins or pectin-like polysaccharides might target Galectin-3 (Gal-3) to impede fibrosis. This research aims to discover novel pectin-like galactan to interfere with fibrosis for potential new drug development. Thus, we purify a novel homogeneous Rhamnogalacturonan-I like polysaccharide with galactan input, XHH2, from the Crocus sativus flower. XHH2 (MW: 35.7 kDa) consists of rhamnose, galacturonic acid, galactose, and arabinose in ratios of 6.6: 6.1: 25.2: 12.1. The backbone of XHH2 comprises 1, 3, 6-Gal and 1, 3, 4-GalA, with branches at O-3 of 1, 3, 6-Gal and O-4 of 1, 3, 4-GalA. O-3 branches include 1, 3-Gal, 1, 4-Gal, 1, 6-Gal, T-Gal, and T-Glc, while O-4 branches consist of 1, 2, 4-Rha, 1, 4-GalA, 1, 5-Ara, T-Ara, T-Gal, and T-α-HexA. Surface plasmon resonance measurement shows that XHH2 binds to both Gal-3 and integrin β1 to block Gal-3/integrin β1 interaction. Mechanism studies further suggest that XHH2 inactivates hepatic stellate cells (HSCs) via disturbing the Gal-3/Integrin-β1/FAK pathway to alleviate liver injury and fibrosis in vitro & in vivo. XHH2 shows a favorable drug safety in the acute toxicity test of oral administration of XHH2 in mice. Overall, XHH2 is an active ingredient against liver fibrosis by targeting the interaction between Gal-3 and Integrin-β1., 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.)

The ever-increasing demand in chemical biology and medicinal research requires the development of new synthetic methods for the rapid construction of libraries of heterocycles from simple raw materials. In this context, the utilization of primary amines or H 2 O as the simple N - or O -sources in the assembly of a heterocyclic ring skeleton is highly desirable from the viewpoint of atom- and step-economy. Herein, we describe a highly efficient three-component reaction of diazo, allylic diacetates, and commercially available anilines (or H 2 O) to access structurally diverse pyrrolidine and tetrahydrofuran derivatives. This formal [1 + 1 + 3] annulation reaction features high efficiency, good yields, and broad functional group compatibility, making it a versatile and robust platform for the (formal) synthesis of several important bioactive molecules. Mechanistic studies suggested that the dirhodium-palladium bimetallic relay catalysis should play a key role in the successive steps of the current reaction, including sequential carbene insertion into the X-H bond and double allylic substitutions, thus allowing for building up molecular complexity from these simple raw materials.

P-stereogenic phosphorus compounds are essential across various fields, yet their synthesis via enantioselective P-C bond formation remains both challenging and underdeveloped. We report the first copper-catalyzed enantioselective hydrophosphorylation of alkynes, facilitated by a newly designed chiral 1,2-diamine ligand. Unlike previous methods that rely on kinetic resolution with less than 50 % conversion, our approach employs a distinct dynamic kinetic asymmetric transformation mechanism, achieving complete conversion of racemic starting materials. This reaction is compatible with a broad range of aromatic and aliphatic terminal alkynes, producing products with high yields (up to 95 %), exclusive cis selectivity, and exceptional regio- and enantioselectivity (>20 : 1 r.r. and up to 96 % ee). The resulting products were further transformed into a diverse array of enantioenriched P-stereogenic scaffolds. Preliminary mechanistic studies were conducted to elucidate the reaction details., (© 2024 Wiley-VCH GmbH.)

Background: Glucagon-like peptide-1 receptor agonists (GLP1RAs) are widely used in manageing type 2 diabetes mellitus and weight control. Their potential in treating ageing-related diseases has been gaining attention in recent years. However, the long-term effects of GLP1RAs on these diseases have yet to be fully revealed., Methods: Using genetic variant in the GLP1R gene to model the long-term effects of GLP1RAs, this Mendelian randomization (MR) study systematically explored potential causal associations between GLP1R agonism and 12 ageing-related diseases and indicators. Genetic summary datasets used in this study were obtained from previous genome-wide association studies., Results: The primary MR analysis results suggested that GLP1R agonism was potentially positively causally associated with appendicular lean mass (Beta = 0.246, 95% CI = 0.096 - 0.396), whole body fat-free mass (Beta = 0.202, 95% CI = 0.048 - 0.355), and lung function (FVC) (Beta = 0.179, 95% CI = 0.152 - 0.205) (p < 0.05). Additionally, a potential negative causal association was observed with myocardial infarction (OR = 0.430, 95% CI = 0.249 - 0.745) (p < 0.05)., Conclusion: The present MR study provides exploratory evidence suggesting potential causal associations between GLP1R agonism and appendicular lean mass, whole-body fat-free mass, lung function (FVC), and myocardial infarction. Given the exploratory nature of these findings and the limitations of the MR methodology, further research is needed to validate these results and investigate the underlying biological mechanisms., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Osteosarcoma (OS), a prevalent metastatic cancer among young individuals, is associated with a grim prognosis. Long non-coding RNAs (lncRNAs), including C1QTNF1-AS1, are pivotal regulators of cancer cell proliferation and motility. As an oncogene, C1QTNF1-AS1 is implicated in various tumor types, such as colorectal, pancreatic, hepatocellular carcinomas, and OS. The aim of this study was to investigate the functions and underlying mechanisms of C1QTNF1-AS1 in the progression of osteosarcoma., Methods: This investigation focused on elucidating the functional roles and mechanisms of C1QTNF1-AS1 in OS cells. Bioinformatics tools were utilized to identify the interaction between microRNA miR-34a-5p and C1QTNF1-AS1, as well as the targeting of LDHA and PDK3 by miR-34a-5p. Dual-luciferase reporter assays and RNA immunoprecipitation were employed to validate these interactions. Expression profiles of C1QTNF1-AS1, miR-34a-5p, LDHA, and PDK3 in osteosarcoma cells were analyzed using RT-PCR and western blot analyses, revealing their intricate relationships. The impact of these molecules on OS cell proliferation, invasion, and migration was assessed through CCK-8, Transwell, and Cell scratch assay. Moreover, the effects on aerobic glycolysis in OS cells were examined by quantifying ATP levels, lactate production, glucose uptake capacity, and the extracellular acidification rate., Results: The findings indicated a significant decrease in C1QTNF1-AS1 expression levels in OS cells compared to normal osteoblasts. A parallel downregulation trend of miR-34a-5p was also observed in OS cells. Silencing C1QTNF1-AS1 led to a marked upregulation of LDHA and PDK3 in OS cells, which was partially attenuated by miR-34a-5p mimics. Functional evaluations demonstrated that suppression of C1QTNF1-AS1 accelerated OS cell growth, motility, invasiveness, and the Warburg effect. Conversely, the overexpression of miR-34a-5p mitigated these stimulatory effects, suggesting a regulatory role in modulating OS progression., Discussion: Our research emphasizes the critical role of C1QTNF1-AS1 in the pathogenesis of osteosarcoma (OS). We discovered that the downregulation of C1QTNF1-AS1 indirectly upregulates the expression of LDHA and PDK3 by suppressing miR-34a-5p, which functions as a regulator of the Warburg effect. This cascade of events promotes OS progression by enhancing glycolytic metabolism and supplying energy for cancer cell growth, migration, and invasion. These findings suggest a potential therapeutic target and highlight the importance of understanding the regulatory network involving lncRNAs in cancer metabolism and progression., 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 © 2025 Zhang, Lun, Zhu, Yang, Ding, Chen, Chang, Gu and Liu.)

Carbohydrates, lipids, bile acids, various inorganic salt ions and organic acids are the main nutrients or indispensable components of the human body. Dysregulation in the processes of absorption, transport, metabolism, and excretion of these metabolites can lead to the onset of severe metabolic disorders, such as type 2 diabetes, non-alcoholic fatty liver disease, gout and hyperbilirubinemia. As the second largest membrane receptor supergroup, several major families in the solute carrier (SLC) supergroup have been found to play key roles in the transport of substances such as carbohydrates, lipids, urate, bile acids, monocarboxylates and zinc ions. Based on common metabolic dysregulation and related metabolic substances, we explored the relationship between several major families of SLC supergroup and metabolic diseases, providing examples of drugs targeting SLC proteins that have been approved or are currently in clinical/preclinical research as well as SLC-related diagnostic techniques that are in clinical use or under investigation. By highlighting these connections, we aim to provide insights that may contribute to the development of improved treatment strategies and targeted therapies for metabolic disorders., Competing Interests: Author YH was employed by Yuhong Pharmaceutical Technology Co., Ltd. The remaining 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 © 2025 Du, Shen, Chen, Yan, Xu, Yang, Yang, Luo, Ding, Hu and He.)

As naturally secreted vesicles by cells, extracellular vesicles (EVs) play essential roles in modulating cell-cell communication and have significant potential in tissue regeneration, immune regulation, and drug delivery. However, the low yield and uncontrollable heterogeneity of EVs have been obstacles to their widespread translation into clinical practice. Recently, it has been discovered that artificial nanovesicles (NVs) produced by cell processing can inherit the components and functions of the parent cells and possess similar structures and functions to EVs, with significantly higher yields and more flexible functionalization, making them a powerful complement to natural EVs. This review focuses on recent advances in the research of artificial NVs as replacements for natural EVs. We provide an overview comparing natural EVs and artificial NVs and summarize the top-down preparation strategies of NVs. The applications of NVs prepared from stem cells, differentiated cells, and engineered cells are presented, as well as the latest advances in NV engineering. Finally, the main challenges of artificial NVs are discussed.

The circadian clock is crucial in plant immunity and metabolism, yet the coordinating mechanisms remain elusive. In the present study, transcriptome analysis of M. oryzae -infected rice leaves and rhythmic analysis showed reduced amplitudes of circadian and phytochrome genes, impacting immune response, metabolic pathways, and calcium signaling. The amplitudes of pattern-triggered immunity (PTI)-related genes declined, while the rhythmicity of effector-triggered immunity (ETI)-related genes disappeared. Moreover, alterations in the phases of metabolic pathways were observed, potentially involved in immune response regulation like phytohormone biosynthesis. Calcium signaling exhibited a circadian pattern similar to that of the whole-transcriptome analysis. The administration of CaCl 2 alleviated, whereas the calcium ion chelator EGTA aggravated, the phenotypes of rice blasts, suggesting their role in regulating the circadian clock-mediated immune response in rice. Our study highlighted the significance of circadian regulation in rice blast-induced immune modulation, which may contribute to developing immunomodulators and the formulation of chronobiology-based precise therapeutic regimens.

Background/Objectives : Genes and environments were transmitted across generations. Parents' genetics influence the environments of their offspring; these two modes of inheritance can produce a genetic nurture effect, also known as indirect genetic effects. Such indirect effects may partly account for estimated genetic variance in T2D. However, the well-established specific genetic risk factors about genetic nurture effect for T2D are not fully understood. This study aimed to investigate the genetic nurture effect on type 2 diabetes and reveal the potential underlying mechanism using publicly available data. Methods : Whole-genome genotyping data of 881 offspring and/or their parents were collected. We assessed SNP-level, gene-based, and pathway-based associations for different types of genetic effects. Results : Rs3805116 (β: 0.54, p = 4.39 × 10 -8 ) was significant for paternal genetic nurture effects. MRPS33 ( p = 1.58 × 10 -6 ), PIH1D2 ( p = 6.76 × 10 -7 ), and SD1HD ( p = 2.67 × 10 -6 ) revealed significantly positive paternal genetic nurture effects. Five ontologies were identified as enrichment in both direct and indirect genetic effects, including flavonoid metabolic process and antigen processing and presentation via the MHC class Ib pathway. Two pathways were only enriched in paternal genetic nurture effects, including the transforming growth factor beta pathway. Tissue enrichment of type 2 diabetes-associated genes on different genetic effect types was performed using publicly available gene expression data from the Human Protein Atlas database. We observed significant gene enrichment in paternal genetic nurture effects in the gallbladder, smooth muscle, and adrenal gland tissues. Conclusions : MRPS33 , PIH1D2 , and SD1HD are associated with increased T2D risk through the environment influenced by paternal genotype, suggesting a novel perspective on paternal contributions to the T2D predisposition.

LiCoO 2 batteries for 3 C electronics demand high charging voltage and wide operating temperature range, which are virtually impossible for existing electrolytes due to aggravated interfacial parasitic reactions and sluggish kinetics. Herein, we report an electrolyte design strategy based on a partially fluorinated ester solvent (i.e., DFEA) that achieves a balance between weak Li + -solvent interactions, sufficient salt dissociation, high interfacial stability, and superior thermal stability to address the aforementioned challenges. The resulting high-voltage wide-temperature electrolyte (HWE) not only possesses low desolvation energy, fast Li + transport, high oxidation stability, excellent thermal-abuse tolerance and non-flammability, but also enables the formation of both inorganic-rich cathode electrolyte interphase (CEI) and solid electrolyte interphase (SEI). Owing to the above merits, this HWE endows the highly stable operation of LiCoO 2 cathodes under an ultra-high voltage of 4.7 V and Graphite || LiCoO 2 batteries in an ultra-wide temperature range of -30 to 70 °C. Meanwhile, a 1.7 Ah-level 4.6 V Graphite || LiCoO 2 pouch cell with a high energy density of 240 Wh kg -1 also delivers excellent cycling stability, representing a significant advancement in the design of electrolytes towards ultra-high voltage and ultra-wide temperature batteries., (© 2025 Wiley-VCH GmbH.)

Pseudokinase TRIB2, a member of the CAMK Ser/Thr protein kinase family, regulates various cellular processes through phosphorylation-independent mechanisms. Dysregulation of TRIB2 has been implicated in promoting tumor growth, metastasis, and therapy resistance, making it a promising target for cancer treatment. In this study, we designed and synthesized a series of TRIB2 PROTAC degraders by conjugating a TRIB2 binder 1 with VHL or CRBN ligands via linkers of varying lengths and compositions. Among these compounds, 5k demonstrated potent TRIB2 degradation with a DC 50 value of 16.84 nM (95 % CI: 13.66-20.64 nM) in prostate cancer PC3 cells. Mechanistic studies revealed that 5k directly interacted with TRIB2, selectively inducing its degradation through a CRBN-dependent ubiquitin-proteasomal pathway. Moreover, 5k outperformed the TRIB2 binder alone in inhibiting cell proliferation and inducing apoptosis, confirming that TRIB2 protein degradation could be a promising therapeutic strategy for TRIB2-associated cancers. Additionally, compound 5k also serves as an effective tool for probing TRIB2 biology., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

HER3 (Human Epidermal Growth Factor Receptor 3) is frequently overexpressed in various cancers, including non-small cell lung cancer (NSCLC), with a prevalence of 83% in primary tumors. Its involvement in tumorigenesis and resistance to targeted therapies makes HER3 a promising target for cancer treatment. Despite being initially considered "undruggable" due to its lack of catalytic activity, significant progress has been made in the development of anti-HER3 therapeutics. Monoclonal antibodies such as lumretuzumab, seribantumab, and patritumab have shown potential in targeting HER3 to overcome resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Additionally, antibody-drug conjugates (ADCs) like HER3-DXd (patritumab deruxtecan) are new drug candidates that have demonstrated selective delivery of cytotoxic chemicals to NSCLC cells by exploiting HER3's widespread expression, minimizing cytotoxicity. This review aims to evaluate the efficacy of current HER3 therapeutics in development and their therapeutic potential in NSCLC, incorporating evidence from clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) is almost always fatal after the failure of asparaginase. This phase II study aimed to investigate the efficacy and safety of tislelizumab combined with gemcitabine and oxaliplatin (Tisle-GemOx) in patients with ENKTCL failing asparaginase., Methods: Eligible patients received Tisle-GemOx as initial induction for 6-8 cycles at 21-day intervals. Responders continued tislelizumab maintenance every two months for two years. The primary endpoint was the best complete response rate (CRR)., Results: As of September 2023, 32 patients were enrolled in our study. Among the 30 efficacy-evaluable patients, the best CRR was 60 %, meeting the primary efficacy endpoint. With a median follow-up of 22.6 months, the median progression-free survival (PFS) was 7.4 months and the 1-year PFS rate was 46.4 %. Subgroup analyses showed that shorter PFS was associated with previous lines of chemotherapy ≥ 2 (P = 0.034) and concomitant hemophagocytic lymphohistiocytosis (P = 0.040). Pseudo-progression was observed in three patients (10 %). The most common grade ≥ 3 toxicities were lymphopenia (25 %) and anemia (15.6 %)., Conclusions: Tisle-GemOx exhibits promising anti-tumor activity and manageable toxicities as a salvage therapy for ENKTCL failing asparaginase. Further long-term follow-up is necessary to evaluate the durability of the response with tislelizumab maintenance in this patient population., 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: To compare the pregnancy and perinatal outcomes of frozen-thawed embryo transfer (FET) in patients following transcervical resection of adhesions (TCRA) versus patients with normal uterine morphology, and to investigate the factors influencing pregnancy outcomes in patients undergoing FET after TCRA., Methods: We retrospectively analyzed FET cycles from September 2014 to September 2023, comparing patients with normal uterine morphology to those with intrauterine adhesions (IUAs) treated with TCRA. Propensity score matching (PSM) adjusted for confounding factors. LASSO regression and multivariate logistic regression identified predictors of outcomes, which were visually represented in nomograms. Model performance was assessed using calibration curves, ROC curves, and DCA, with bootstrap method for internal validation., Results: Post-PSM analysis showed higher live birth rates in patients with normal uterine morphology after clinical pregnancy (75.1% vs. 61.7%, P < 0.001). No significant differences were noted in clinical pregnancy rates and perinatal outcomes between the groups. Factors influencing clinical pregnancy in FET after TCRA included basal progesterone levels, endometrial thickness, parity, infertility cause, embryo stage at transfer, number and quality of embryos transferred, IUA severity, and TCRA surgical procedures. Body mass index, basal LH levels, and day 14 HCG levels post-embryo transfer were determinants of live birth outcome., Conclusion: FET cycles following TCRA showed a lower rate of successful live births, but TCRA did not increase adverse perinatal outcome risks. Our study introduces an innovative predictive model for clinical pregnancy and live birth outcomes in patients undergoing FET following TCRA, addressing a significant void in existing research., (© 2024 International Federation of Gynecology and Obstetrics.)

The interplay between biomaterials and host immune responses critically determines outcomes in tissue restoration. Recent studies suggest that physicochemical properties of materials can dictate pro-regenerative versus pro-fibrotic responses and have begun to define the key immune cell types and signals governing these divergent effects. This emerging understanding enables the engineering of regenerative biomaterials capable of functional restoration in situ. An injectable nanofiber-hydrogel composite (NHC) microparticles are designed and constructed from cross-linked electrospun collagen nanofiber fragments surface-bonded to the hyaluronic acid hydrogel network via covalent conjugation during the cross-linking process. The collagen nanofiber fragments, acting as the structural reinforcement component, increased the overall storage modulus of the NHC to a level comparable to native soft tissues while maintaining a sufficiently high degree of porosity of the hydrogel phase to allow host cell infiltration following subcutaneous injection of the NHC microparticles. More importantly, the NHC promoted macrophage/monocyte infiltration, migration, and spreading, sustained cell recruitment over time, and enhanced the proangiogenic effect and recruitment of PDGFRα + perivascular progenitor cells, leading to extensive adipose tissue remodeling. This study demonstrates the regenerative potential of the injectable NHC microgels as an off-the-shelf solution for devastating soft tissue losses., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Identifying antigen-specific T cells from tumor-infiltrating lymphocytes is essential for designing effective T cell immunotherapies. Traditional methods can detect antigen-specific T cells but struggle with high-throughput screening and multimodal profiling simultaneously. To address this issue, we developed DropCCI, a new strategy that transfers antigen information to co-incubated T cells for high-throughput, non-contaminated multimodal profiling. In DropCCI, droplets encapsulated DNA barcodes and antigen-loaded antigen-presenting cells (APCs), while click chemistry-modified T cells were injected into these droplets to capture free barcodes and acquire the corresponding antigen information. Following cell-cell interaction, APCs were removed via streptavidin-biotin conjugation, to prevent contamination. The resulting T cells underwent single-cell omics sequencing for comprehensive profiling of their antigen specificity, transcriptome, and genomics accurately. This click-chemistry method allowed detection of antigen-specific T cells without lysing APCs, avoiding cross-cell contamination and enabling low-noise multimodal profiling of primary T cells. With a completion time within 12 h and no requirement for complex equipment, DropCCI provides unbiased single-cell sequencing results that offer a comprehensive understanding of anti-tumor T cell responses. The concept of DropCCI holds great promise not only for advancing the field of T cell immunotherapy but also for its potential application in studying other cell-cell interactions., Competing Interests: Declaration of competing interest Zhong Qiang Ding was an investigator of Merry Electronics (Singapore) Co. Ltd., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Higher blood pressure has been proven to be associated with poorer functional outcomes after successful reperfusion by EVT. However, the effect of intensive blood pressure-lowering regimens in these patients remains controversial and ambiguous in clinical practice. We propose further analysis aimed at determining the effect of an intensive blood pressure-lowering regimen after EVT in AIS., Methods: The protocol registered in PROSPERO CRD42023360989. We performed a systematic search that was comprehensively executed in online databases for studies published up to June 2022. Eligibility criteria were established based on the PICOS model. The Cochrane risk of bias algorithm was used to evaluate the risk of bias. The effect models were applied to calculate the pooled ORs and CIs via Review Manager 5.4 software., Results: A total of 1582 citations were identified, 3 randomized clinical trials and 2 retrospective cohort studies were included. Data from 3211 patients were analyzed. We revealed that intensive blood pressure-lowering interventions could significantly reduce symptomatic intraparenchymal hemorrhage compared with standard blood pressure lowering. Nevertheless, favorable functional outcome, poor outcome, all-cause mortality within 3 months and intraparenchymal hemorrhage in 24 hours showed no significant differences. Subgroup analysis revealed the variability of systolic blood pressure within 24 hours after EVT was not associated with odds of poor outcome and intraparenchymal hemorrhage., Conclusions: Based on the current evidence, intensive blood pressure-lowering regimen was superior to standard blood pressure-lowering regimen for a reduced risk of symptomatic intraparenchymal hemorrhage in AIS patients treated with EVT, but there was no statistically significant difference found between the 2 regimens for the other outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Buddleja officinalis has been used as a traditional Chinese medicine for years. Although evidence has demonstrated it can enhance liver function, the active material basis remains unknown. We hypothesize polysaccharides from Buddleja officinalis may be the active material against liver disease. Herein, we elucidated the structure of a novel pectin-like polysaccharide designed BOM0.05S2 with a molecular weight of 13.6 kDa. Combined with endo-1, 4-β-Mannanase degradation, we found its backbone consists of alternate 1, 2, 4-linked α-Rhap and 1, 4-linked α-GalpA (RG-I type pectin) and mannoglucan, with branches of 1, 4-, 1, 6- and 1, 3, 6-linked β-Galp, T-, 1, 5- and 1, 3, 5-linked α-Araf, T-linked β-Manp and T-linked α-Glcp substituted at C-4 of 1, 2, 4-linked α-Rhap and C-6 of 1, 4, 6-linked α-Glcp. As speculated, BOM0.05S2 showed a significant improvement on carbon tetrachloride (CCl 4 )-induced liver damage in mice. Bioactivity test showed that BOM0.05S2 reduced AST, ALT and four indexes of liver fibrosis including LN, HA, IV-C, PC-III. Further, we demonstrated that BOM0.05S2 attenuated the collagenous fiber and α-SMA in liver. These findings highlight the potential of BOM0.05S2 as a lead compound for the treatment of liver fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Immune response plays an important role in the regulation of elderly hip fracture. This study aims to analyze the relationship between systemic inflammatory markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) and mortality and walking independence, providing valuable references for the postoperative management of geriatric hip fracture., Methods: A retrospective analysis of prospective data on elderly patients who have undergone hip surgery and have been followed for at least one year. The receiver operating characteristic (ROC) curves and the optimum cutoff value were calculated. Univariate analysis and multivariate logistic regression analysis were used to identify the associations between admission four systemic inflammatory markers and one-year mortality and locomotion recovery., Results: During the study period, respiratory disease was the most common cause of death, followed by cardiovascular disease. Multivariate analysis identified NLR (OR, 1.13; 95%CI: 1.09-1.17), SIRI(OR, 1.18; 95%CI: 1.08-1.28) and advanced age (OR, 1.06; 95%CI: 1.01-1.11) as independent risk factors for one-year mortality. In addition, 89 (rate, 31.8%) survivors had poor walking independence within one year. NLR (OR, 1.37; 95%CI: 1.26-1.50), SII(OR, 1.00; 95%CI: 1.001-1.003), SIRI(OR, 1.36; 95%CI: 1.18-1.57) and advanced age (OR, 1.08; 95%CI: 1.02-1.13) were associated with postoperative locomotion recovery., Conclusions: In summary, admission NLR and SIRI are correlated with a high risk of one-year walking independence and mortality, providing a basis for the clinical management of geriatric hip fractures., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the ethics committee of the Third Hospital of Hebei Medical University. Informed consent was obtained from all the participants. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)