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Xin Tang,1,* Qifu Li,1,* Gaoyangzi Huang,1 Ziwen Chen,2 Ya Huang,1 Xianmei Pei,1 Siwen Zhao,1 Zili Liu,1 Taipin Guo,1 Fanrong Liang2 1School of Second Clinical Medicine/The Second Affiliated Hospital, Yunnan University of Chinese Medicine, Kunming, People’s Republic of China; 2College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Taipin Guo, School of Second Clinical Medicine/The Second Affiliated Hospital, Kunming, People’s Republic of China, Email gtphncs@126.com Fanrong Liang, College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Email acuresearch@126.comPurpose: Acute lumbar sprain (ALS) is a common clinical disease characterized by persistent intolerable low back pain and limitation of movement, and quick pain relief and restoration of mobility in a short time are the main needs of patients when they visit the clinic. This study aims to evaluate the immediate efficacy of contralateral acupuncture (CAT) on SI3 combined with active exercise in treating ALS.Methods and Analysis: This study is a randomized controlled trial which will recruit 118 eligible participants aged 18 to 55 years with ALS at the Second Affiliated Hospital of Yunnan University of Chinese Medicine between March 2024 and December 2026. Participants will be randomly assigned to the acupuncture group or the sham-acupuncture group in a 1:1 ratio. The acupuncture group will receive a 10-minute acupuncture treatment combined with active exercise, while the sham-acupuncture group will receive a 10-minute sham acupuncture treatment combined with active exercise. Randomization will use a computer-generated sequence with allocation concealed in opaque envelopes. The primary outcome will be the pain visual analogue scale (VAS) scores after 10 minutes of treatment. Secondary outcomes will include the pain VAS scores at other time points (2, 4, 6, and 8 minutes post-treatment), the lumbar range of motion (ROM) scores at various time points, blinded assessment, the treatment effect expectancy scale, and the rescue analgesia rate. The analysis will follow the intention-to-treat principle. The primary outcome will be analyzed using ANCOVA, and secondary outcomes with repeated measures ANOVA. The rescue analgesia rate will be assessed using either the χ2 test or Fisher’s exact test.Discussion: This study is the first randomized controlled trial to assess the immediate efficacy of CAT in combination with active exercise for ALS. This study will provide a simple, rapid, and effective treatment for the clinical management of ALS.Keywords: acute lumbar sprain, immediate efficacy, contralateral acupuncture, active exercise, randomized controlled trial

Chunyan Yang,&ast; Hao Tian,&ast; Guixing Xu, Qin Luo, Mingsheng Sun, Fanrong Liang Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fanrong Liang, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, No. 37 Shi’er Qiao Road, Chengdu, Sichuan, 610075, People’s Republic of China, Email acuresearch@126.comPurpose: The effect of acupuncture as adjunctive therapy for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) was controversial. Thus, we aimed to evaluate the effects of acupuncture for treating AECOPD.Methods: Eight databases were searched from database inception to July 30, 2023. All RCTs compared acupuncture plus conventional western medicine with conventional western medicine alone were included. Outcomes were quality of life, lung function, blood oxygen condition, exercise capacity, daily symptoms, duration of hospitalization, and adverse events. The statistical analyses were conducted using Stata 17.0, and methodological quality was measured by the Cochrane bias risk assessment tool. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence.Results: Twelve studies including 915 patients were included. Compared with conventional western medicine alone, acupuncture combined with conventional western therapy significantly improved quality of life (CAT: MD: − 3.25; 95% CI: − 3.73 to − 2.78, P< 0.001) and arterial blood gas (PaCO2: MD: − 1.85; 95% CI: − 2.74 to − 0.95, P< 0.001; PaO2: MD: 5.15; 95% CI: 1.22 to 9.07, P = 0.01). And for lung function, statistical benefits were found in FEV1/FVC (MD: 4.66; 95% CI: 2.21 to 7.12, P< 0.001), but no difference was seen for FEV1% (MD: 1.83; 95% CI: − 0.17 to 3.83, P = 0.073). There was no significant improvement in exercise capacity (6MWD: MD: 96.69; 95% CI: − 0.60 to 193.98, P = 0.051), hospitalization duration (MD: − 5.70; 95% CI: − 11.97 to 0.58, P = 0.075), and dyspnea (mMRC: MD: − 0.19; 95% CI: − 0.61 to 0.63, P = 0.376) between two groups. Overall bias for CAT and mMRC was in “high” risk, FEV1%, FEV1/FVC, PaCO2, and PaO2 was in “some concern” and 1 RCT assessing hospitalization duration was in “low” risk. And the overall assessments were either moderate, low or very low certainty. Seven trials performed safety assessment of acupuncture, and no serious adverse events were reported.Conclusion: Acupuncture might have auxiliary effects on AECOPD. However, the quality of the evidence is limited, and more high-quality RCTs are needed to be performed in the future.Keywords: acute exacerbation of chronic obstructive pulmonary disease, acupuncture, systematic review, meta-analysis

Long-term tumour recurrence rates and complications of endoscope-assisted partial superficial parotidectomy (PSP) are rarely reported compared to traditional open approaches. This retrospective study included 306 patients with superficial parotid benign neoplasms who were divided into an endoscopy group (endoscope-assisted PSP, n = 102) and a control group (conventional PSP, n = 204). There were no significant differences in clinical and pathological characteristics between the two groups, except age (P = 0.001). Three patients had confirmed recurrence during a mean follow-up duration of 125.1 months. Ten (9.8%) patients in the endoscopy group and 22 (10.8%) in the control group developed transient facial nerve palsy (P = 0.792), and recovered 6 months after the operation. Nine (8.8%) and 19 (9.3%) patients, respectively, suffered from Frey syndrome (P = 0.889). A sensory deficit of the auricle occurred in 24 (23.5%) and 57 (27.9%) patients respectively (P = 0.410). Patients in the endoscopy group were more satisfied with the postoperative scar than those in the control group (P < 0.001). This study demonstrated that the endoscope-assisted PSP can be curative, with better cosmetic outcomes than the conventional approach, and does not increase the incidence of postoperative complications or the local recurrence rate. [ABSTRACT FROM AUTHOR]

Soil thallium (Tl) contamination is of major public concern but little is known about soil Tl ecological toxicity or potential ecological remediation strategies. Here, two soil animal species with different ecological niches, Folsomia candida and Enchytraeus crypticus, were used to test Tl toxicity and modification by exogenous organic materials (i.e. maize straw and biochar). The endpoints of Tl ecotoxicity to F. candida and E. crypticus were studied at two biological levels, i.e., the individual (body Tl concentrations) and the population (survival, reproduction, and growth). Thallium concentrations in F. candida and E. crypticus increased with increasing soil Tl concentration, and their survival and reproduction rates decreased with increasing soil Tl concentration. The LC50 value of Tl effects on F. candida mortality (28 d) was 24.0 mg kg -1 and the EC50 value of reproduction inhibition was 6.51 mg kg -1 . The corresponding values were 4.15 mg kg -1 and 2.31 mg kg -1 respectively for E. crypticus showing higher sensitivity to soil Tl than F. candida. These effective values are comparable to or much lower than the environmental Tl concentrations in field soils, suggesting high potential ecological risk. Both biochar and straw can decrease animal body Tl concentrations in different ways, i.e. reducing Tl availability or offering clean food sources, and addition of exogenous organic materials clearly mitigated Tl ecotoxicity in highly polluted soil. The results highlight the potential Tl ecological risk to soil animals and the potential use of organic materials to control the toxicity., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Lung ischemia-reperfusion injury (LIRI) poses a significant challenge in various clinical scenarios. Despite extensive research on the pathogenesis and potential treatments of LIRI, there is a notable absence of bibliometric analysis., Materials and Methods: We summarized the results of LIRI research through two searches on the Web of Science, covering data from 1979 to 2023 with topic words "lung" and "reperfusion injury". The collected data were analyzed and visualized based on country, author(s), and keywords by bibliometric software. The keyword "programmed cell death" was further added to explore the hotspot of the LIRI research field., Results: The initial analysis of 1648 research articles showed a total of 40 countries and 7031 researchers were involved in the publications, with America being the most productive country in the research field of LIRI. Keyword analysis revealed that the evolving focus of LIRI research has progressively transitioned from, lung transplantation, primary graft dysfunction, inflammation, oxidative stress, and ex vivo lung perfusion to cell death. Subsequently, 212 publications specifically addressing programmed cell death (PCD) in LIRI were identified, which clarified the recent hotspot of the LIRI field., Conclusion: With closer international cooperation and increasing research scale, the LIRI research focused mainly on the pathogenesis and potential therapeutic interventions for LIRI. PCD in LIRI is becoming a trending topic and will continue to be a hotspot in this field. Our study may offer valuable guidance for future research endeavors concerning LIRI., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cerebral cavernous malformation (CCM) is a low-flow, bleeding-prone vascular disease that can cause cerebral hemorrhage, seizure and neurological deficits. Its inheritance mode includes sporadic or autosomal dominant inheritance with incomplete penetrance, namely sporadic CCM (SCCM) and familial CCM. SCCM is featured by single lesion and single affection in a family. Among CCM patients especially SCCM, the pathogenesis of the corresponding phenotypes and pathological features or candidate genes have not been fully elucidated yet., Methods: Here, we performed in-depth single-cell RNA sequencing (scRNA-Seq) and bulk assay for transposase-accessible chromatin sequencing (ATAC-Seq) in SCCM and control patients. Further validation was conducted for the gene of interest using qPCR and RNA in situ hybridization (RNA FISH) techniques to provide further atlas and evidence for SCCM generative process., Results: We identified six cell types in the SCCM and control vessels and found that the expression of NEK1, RNPC3, FBRSL1, IQGAP2, MCUB, AP3B1, ESCO1, MYO9B and PVT1 were up-regulated in SCCM tissues. Among the six cell types, we found that compared with control conditions, PVT1 showed a rising peak which followed the pseudo-time axis in endothelial cell clusters of SCCM samples, while showed an increasing trend in smooth muscle cell clusters of SCCM samples. Further experiments indicated that, compared with the control vessels, PVT1 exhibited significantly elevated expression in SCCM samples., Conclusion: In SCCM conditions, We found that in the process of development from control to lesion conditions, PVT1 showed a rising peak in endothelial cells and showed an increasing trend in smooth muscle cells at the same time. Overall, there was a significantly elevated expression of NEK1, RNPC3, FBRSL1, IQGAP2, MCUB, AP3B1, ESCO1, MYO9B and PVT1 in SCCM specimens compared to control samples., 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: With the rapid development of information and communications technology, the prevalence of cyberbullying and its influences on mental health among college students have received increasing attention. The purpose of this study was to survey the prevalence of cyberbullying in Chinese college students and to investigate the association between cyberbullying, emotional exhaustion and the perception of collective efficacy., Methods: The study sample included 5315 respondents from ten different colleges in Liaoning Province. Their demographic characteristics and characteristics of online behaviors and instruments including a Cyberbullying Scale with 12 items, the Emotional Exhaustion measuring scale, and the Perception of Collective Efficacy Scale, were employed., Results: The prevalence of cyberbullying victimization was 26.45 % (1406/5315). Younger male college students who had more active online lives were more likely to be cyberbullying victims. Binary logistic regression analysis showed that being a cyberbullying victim (odds ratio, OR = 2.188; 95%CI, 1.841-2.600, p < 0.001) was associated with emotional exhaustion. Perceptions of collective efficacy (PCE) is negatively associated with cyberbullying and, thus, alleviate emotional exhaustion and mediate the negative effect of emotional exhaustion after it occurs., Conclusion: Cyberbullying occurs quite frequently among Chinese college students. Cyberbullying is a predictor of emotional exhaustion. PCE play a bidirectional role before and after cyberbullying occurs. Our study highlights the importance of the identification of potential cyberbullying victims and of the provision of early interventions in cyberbullying among Chinese college students to improve their mental health., Competing Interests: Declaration of competing interest All authors declare no conflict of interest in the conducting this study., (Copyright © 2024. Published by Elsevier B.V.)

Designing and constructing the active center of Ru-based catalysts is the key to efficient hydrolysis of ammonia borane (NH 3 BH 3 , AB) for hydrogen production. Herein, V-doped Ru/Ti 2.5 V 0.5 C 2 dual-active center catalysts were synthesized, showing excellent catalytic ability for AB hydrolysis. The corresponding turnover frequency value was 1072 min -1 at 298 K, and the hydrolysis rate r B of AB was 235 × 10 3 mL·min -1 ·g Ru -1 . X-ray photoelectron spectroscopy results indicated that the interaction between V-doped Ti 3 C 2 and catalytic metal Ru transfers electrons from Ti to Ru, resulting in electron-rich Ru species. According to density functional theory calculations, the activation energy and reaction dissociation energy of the reactants AB and H 2 O on V-doped catalysts were lower than those of Ru/Ti 3 C 2 , thus optimizing the catalytic kinetics of AB hydrolysis. The modification strategy of V-doped Ti 3 C 2 provides a new pathway for the development of high-performance catalysts for AB hydrolysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Periodontitis is a chronic infectious disease that affects the oral health of adults. Periodontal stem cells (PDLSCs) have good self-renewal and multipotential differentiation abilities to maintain the integrity of periodontal support structure and repair defects. This study aimed to elucidate the role of peroxisome proliferator activated receptor-γ co-activator 1-α (PGC-1α) in lipopolysaccharide (LPS)-induced PDLSCs and the underlying mechanisms related to predicated that pyrin domain (PYD)-only protein 1 (POP1). Notably downregulated PGC-1α and POP1 expression was observed in LPS-induced PDLSCs. PGC-1α or POP1 overexpression significantly reduced the inflammation and enhanced the osteogenic differentiation of LPS-treated PDLSCs. Particularly, PGC-1 bound to POP1 promoter region and upregulated POP1 expression. Moreover, POP1 knockdown ameliorated the impacts of PGC-1α overexpression on the inflammation and osteogenic differentiation in LPS-induced PDLSCs. Besides, PGC-1α inactivated NLRP3 signaling in LPS-treated PDLSCs, which was reversed by POP1 knockdown. Taken together, PGC-1α inhibits NLRP3 signaling through transcriptional activation of POP1, thereby alleviating inflammation and strengthening osteogenic differentiation of LPS-induced PDLSCs., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Tumor spheroids are widely studied for in vitro modeling of tumor growth and responses to anticancer drugs. However, current methods are mostly limited to static and perfusion-based cultures, which can be improved by more accurately mimicking pathological conditions. Here, we developed a diffusion-based dynamic culture system for tumor spheroids studies using a thin membrane of hydrogel microwells and a microfluidic device. This allows for effective exchange of nutrients and metabolites between the tumors and the culture medium flowing underneath, resulting in uniform tumor spheroids. To monitor the growth and drug response of the spheroids in real-time, we performed spectroscopic analyses of the system's impedance, demonstrating a close correlation between the tumor size and the resistance and capacitance of the system. Our results also indicate an enhanced drug effect on the tumor spheroids in the presence of a low AC electric field, suggesting a weakening mechanism of the spheroids induced by external perturbation., 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.)

In unmanned aircraft applications, electromagnetic wave (EMW) absorbers suffer from defects in narrow absorption bands and poor mechanical properties. To solve the problems, a lightweight multilayer stealth structure with wide broadband absorption performance and excellent mechanical properties was designed and prepared by adjusting microscopically the number of multi-walled carbon nanotubes (MWCNT) and modulating macroscopically the thickness-matching relationship of the structure to promote the absorption of EMW synergistically. Under the MWCNT of 30 wt% and the depletion layer with the thickness of 0.2 mm, the effective absorption bandwidth (EAB) covers the entire Ku-band while maintaining a minimum reflection loss (RL) of -15 dB. Besides, the radar cross-sectional area attenuation is as high as 23.1 dBm 2 , as well as the mechanical properties of the radar absorbing structures (RAS) were improved significantly due to the reducing structural density from balsa wood and the enhancement effect of glass fiber mats (GFM). The study constructed balsa-based RAS with excellent EMW absorbing and mechanical properties from both micro-nano scale and macro-structure, providing a research route for designing high-performance and lightweight stealth structures., 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.)

Emu oil is the oil extracted from the body fat of the Australian bird emu. Although previous studies have reported that emu oil has anti-inflammatory effects, the effect and mechanism of emu oil on the treatment of atopic dermatitis have not been reported. Here, 2, 4-dinitrofluorobenzene was used to induce atopic dermatitis-like appearance on the back skin of C57BL/6 mice. And then, the effect of emu oil in the atopic dermatitis treatment was evaluated. We found that emu oil reduced the transdermal water loss in the atopic dermatitis model. Additionally, the epidermal thickness treated with emu oil was significantly thinner. The number of mast cells and inflammatory cells were significantly decreased. The thymic stromal lymphopoietin (TSLP), which is secreted by keratinocyte, was decreased significantly after treatment. Moreover, the serum levels of cytokines TSLP, interleukin-4, interleukin-13, and immunoglobulin (Ig) E were decreased after emu oil treatment. Surprisingly, we found that the high level of Cdc42 expression in the atopic dermatitis, which was decreased after emu oil treatment. To detect the role of Cdc42 in atopic dermatitis, we constructed atopic dermatitis model in mice with sustained activation of Cdc42 signaling. Furthermore, we have confirmed that emu oil demonstrates anti-inflammatory effects in atopic dermatitis by inhibiting the expression of Cdc42 signaling in keratinocytes. In conclusion, we discovered a new role of Cdc42 in the development of atopic dermatitis, which mediated the therapeutic effect of emu oil on atopic dermatitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Exposure to a hypobaric hypoxic environment at high altitudes can lead to lung injury. In this study, we aimed to determine whether curcumin (Cur) could improve lung barrier function and protect against high-altitude-associated acute lung injury., Methods: Two hundred healthy rats were randomly divided into standard control, high-altitude control (HC), salidroside (40 mg/kg, positive control), and Cur (200 mg/kg) groups. Each group was further divided into five subgroups. Basic vital signs, lung injury histopathology, routine blood parameters, plasma lactate level, and arterial blood gas indicators were evaluated. Protein and inflammatory factor (tumor necrosis factor α (TNF-α), interleukin [IL]-1β, IL-6, and IL-10) concentrations in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method and enzyme-linked immunosorbent assay, respectively. Inflammation-related and lung barrier function-related proteins were analyzed using immunoblotting., Results: Cur improved blood routine indicators such as hemoglobin and hematocrit and reduced the BALF protein content and TNF-α, IL-1β, and IL-6 levels compared with those in the HC group. It increased IL-10 levels and reduced pulmonary capillary congestion, alveolar hemorrhage, and the degree of pulmonary interstitial edema. It increased oxygen partial pressure, oxygen saturation, carbonic acid hydrogen radical, and base excess levels, and the expression of zonula occludens 1, occludin, claudin-4, and reduced carbon dioxide partial pressure, plasma lactic acid, and the expression of phospho-nuclear factor kappa., Conclusions: Exposure to a high-altitude environment for 48 h resulted in severe lung injury in rats. Cur improved lung barrier function and alleviated acute lung injury in rats at high altitudes., (© 2024. The Author(s).)

Stepping movement is delta (1-4 Hz) rhythmic and depends on sensory inputs. Stepping-related delta-rhythmic neural activity is coupled to beta (10-30 Hz) frequency dynamics that are also prominent in sensorimotor circuits. We explored how beta-frequency sensory stimulation influences stepping and dorsal striatal regulation of stepping. We delivered audiovisual stimulation at 10 or 145 Hz to mice voluntarily locomoting, while recording locomotion, cellular calcium dynamics and local field potentials (LFPs). We found that 10 Hz, but not 145 Hz stimulation prominently entrained striatal LFPs. Even though stimulation at both frequencies promoted locomotion and desynchronized striatal network, only 10 Hz stimulation enhanced the delta rhythmicity of stepping and strengthened the coupling between stepping and striatal LFP delta and beta oscillations. These results demonstrate that higher frequency sensory stimulation can modulate lower frequency striatal neural dynamics and improve stepping rhythmicity, highlighting the translational potential of non-invasive beta-frequency sensory stimulation for improving gait., (© 2024. The Author(s).)

Emulsified asphalt mixtures' cold mix and paving features facilitate asphalt pavements in fulfilling dual-carbon and energy-saving demands. Anionic emulsifiers can enhance emulsion stability, ensure uniform dispersion of oil and water, possess good decompression viscosity, thickening, and lubricating properties, and maintain good stability under acidic conditions. Nevertheless, anionic emulsified asphalt is restricted in engineering applications due to problems like its storage stability. In this paper, eight anionic emulsifiers and two preparation procedures were chosen for stability tests. Through static tests, storage tests, sieve residue tests, and laser particle size tests, the impacts of emulsifiers on the storage stability and dispersion of asphalt were analyzed. Waterborne epoxy resin exhibits excellent adhesive properties, mechanical properties, chemical resistance, and heat stability. A fluorescence microscope test, static and storage test, laser particle size test, and cementation test were employed to explore the effects of different preparation processes and waterborne epoxy mixing ratios on emulsified asphalt's storage stability, dispersion stability, and structural stability. The results showed that: (1) the emulsified asphalt prepared with the BWH-02 emulsifier exhibits the best storage stability, and blending with 20% of the waterborne epoxy modifier can notably enhance the bonding properties; (2) the shear strength of the BWH-02 waterborne epoxy emulsified asphalt prepared can reach 1.543 MPa, and the tensile viscosity can reach 0.848 MPa; (3), The emulsified asphalt prepared by the process of modification has better storage stability than that prepared by the side of the emulsification process. Moreover, the storage stability of emulsified asphalt prepared by emulsification and modification is superior to that of the emulsification and modification process. This research provides theoretical and technical support for popularizing and applying cold-mixed cold-paving asphalt mixtures., (© 2024. The Author(s).)

Background: The pathogenesis of Crohn's disease involves genetic and environmental factors, with the gut microbiome playing a crucial role. The Crohn's disease-associated variant rs13107325 in the SLC39A8 gene results in an A391T substitution in the ZIP8 metal ion transporter and has previously been linked to alterations in the colonic microbiome in variant carriers. We hypothesized that the A391T substitution alters metal ion homeostasis in the colonic mucosal-luminal interface, thereby inducing dysbiosis which may promote intestinal inflammation., Methods: To evaluate this hypothesis, we generated a SLC39A8 A393T mouse model (matching human A391T). We first examined trace element abundance in the colonic mucosal epithelium and lumen of homozygous A393T and wild-type (WT) mice to determine if the variant affected metal distribution. We also performed 16S rRNA gene sequencing on colon samples at 2 months, 3-4 months, and 12 months of age, and conducted histological scoring of colon tissue collected from 5-month and 10-month old mice., Results: Consistent with an effect of the variant on ZIP8 function, homozygous A393T mice exhibited increased cobalt in the colonic mucosa, but reduced iron, zinc, manganese, cobalt, copper, and cadmium in the colonic lumen. 16S rRNA gene sequencing of colon samples revealed variant-linked effects on microbiome beta diversity in 2-month-, 3-4-month-, and 12-month-old mice. Histological scoring showed spontaneous intestinal inflammation in 10-month but not in 5-month-old mice. Lastly, predicted pathway analysis of the microbiome samples revealed differential enrichment of iron-, zinc-, and cobalt-dependent pathways in A393T mice compared to wild-type controls., Conclusion: These results suggest that the variant in SLC39A8 primarily restricts metal availability to the microbiota, resulting in compositions that can adapt to the environment and that A393T-linked dysbiosis occurs prior to the onset of inflammation. This study paves the way for future studies investigating risk variants as microbiome-disease modifiers., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) represents an aggressive subtype of HCC and is associated with poor survival., Purpose: To investigate the performance of a representation learning-based feature fusion strategy that employs a multiphase contrast-enhanced CT (mpCECT)-based latent feature fusion (MCLFF) model for MTM-HCC identification., Methods: A total of 206 patients (54 MTM HCC, 152 non-MTM HCC) who underwent preoperative mpCECT with surgically confirmed HCC between July 2017 and December 2022 were retrospectively included from two medical centers. Multiphasic radiomics features were extracted from manually delineated volume of interest (VOI) of all lesions on each mpCECT phase. Representation learning based MCLFF model was built to fuse multiphasic features for MTM HCC prediction, and compared with competing models using other fusion methods. Conventional imaging features and clinical factors were also evaluated and analyzed. Prediction performance was validated by ROC analysis and statistical comparisons on an internal validation and an external testing dataset., Results: Fusion of radiomics features from the arterial phase (AP) and portal venous phase (PAP) using MCLFF demonstrated superior performance in MTM HCC prediction, with a higher AUC of 0.857 compared with all competing models in the internal validation set. Integration of multiple radiological or clinical features further improved the overall performance, with the highest AUCs of 0.857 and 0.836 respectively achieved in the internal validation and external testing set., Conclusions: Multiphasic radiomics features of AP and PVP fused by the MCLFF have demonstrated substantial potential in the accurate prediction of MTM HCC. Clinical factors and Radiological features in mpCECT contribute incremental values to the developed MCLFF strategy., (© 2024 American Association of Physicists in Medicine.)

Background: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC)., Methods: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS)., Results: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide(EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs. 12.3 months (hazard ratio [HR]: 0.38, 95% CI: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs. 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs. 14.7 months) and PFS (9.1 months vs. 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs. 13.7 months and median PFS of 9.8 months vs. 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs. 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs. 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade., Conclusion: Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Clubroot has become a major obstacle in rapeseed production. Breeding varieties resistant to clubroot is the most effective method for disease management. However, the clubroot-resistant germplasm of rapeseed remains limited. To tackle this challenge, we synthesized the clubroot-resistant mustard, CT19, via distant hybridization, and subsequently an F 2 segregating population was created by intercrossing CT19 with a clubroot-susceptible germplasm CS15. A major-effect clubroot resistance QTL qCRa3-1 on chromosome A03 was identified through QTL scanning. Transcriptome analyses of CT19 and CS15 revealed that the mechanisms conferring resistance to Plasmodiophora brassica likely involved the regulation of flavonoid metabolism, fatty acid metabolism, and sulfur metabolism. By combining the results from transcriptome, QTL mapping, and gene sequencing, a candidate gene BjuA03.BNT1, encoding NLR (nucleotide-binding domain leucine-rich repeat-containing receptors) protein, was obtained. Intriguingly, comparing with CT19, a base T insertion was discovered in the BjuA03.BNT1 gene's coding sequence in CS15, resulting an alteration within the LRR conserved domain. Overexpression of BjuA03.BNT1 from CT19 notably enhanced the resistance to clubroot in Arabidopsis. Our investigations revealed that BjuA03.BNT1 regulated the resistance to clubroot by modulating fatty acid synthesis and the structure of cell wall. These results are highly relevant for molecular breeding to improve clubroot resistance in rapeseed., 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. Declaration of competing interest The authors declare that they have no competing interests. Conflict of interest The authors state that there is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Physicians and patients are eager to know likely functional outcomes at different stages of treatment after acute ischemic stroke (AIS). The aim of this study was to develop and validate a 2-step model to assess prognosis at different time points (pre- and posttreatment) in patients with AIS having endovascular thrombectomy (EVT)., Methods: The prediction model was developed using a prospective nationwide Chinese registry (ANGEL-ACT). A total of 1676 patients with AIS who underwent EVT were enrolled into the study and randomly divided into development (n=1351, 80%) and validation (n=325, 20%) cohorts. Multivariate logistic regression, least absolute shrinkage and selection operator regression, and the random forest recursive feature elimination algorithm were used to select predictors of 90-day functional independence. We constructed the model via discrimination, calibration, decision curve analysis, and feature importance., Results: The incidence of 90-day functional independence was 46.3% and 40.6% in the development and validation cohorts, respectively. The area under the curve (AUC) for model 1 which included 5 pretreatment predictors (age, admission National Institutes for Health Stroke Scale score, admission glucose level, admission systolic blood pressure, and Alberta Stroke Program Early Computed Tomography score) was 0.699 (95% confidence interval [CI], 0.668-0.730) in the development cohort and 0.658 (95% CI, 0.592-0.723) in the validation cohort. Two treatment-related predictors (time from stroke onset to puncture and successful reperfusion) were added to model 2 which had an AUC of 0.719 (95% CI, 0.688-0.749) and 0.650 (95% CI, 0.585-0.716) in the development cohort and validation cohorts, respectively., Conclusions: The 2-step prediction model could be useful for predicting the functional independence in patients with AIS 90-days after EVT., Competing Interests: R.H. is a member of the Editorial Board of the Journal of Neurosurgical Anesthesiology. The remaining authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Skin aging has been associated with the onset of various skin issues, and recent studies have identified an increase in Cdc42 activity in naturally aging mice. While previous literature has suggested that CASIN, a specific inhibitor of Cdc42 activity, may possess anti-aging properties, its specific effects on the epidermis and dermis, as well as the underlying mechanisms in naturally aging mice, remain unclear. Our study revealed that CASIN demonstrated the ability to increase epidermal and dermal thickness, enhance dermal-epidermal junction, and stimulate collagen and elastic fiber synthesis in 9-, 15-, and 24-month-old C57BL/6 mice in vivo. Moreover, CASIN was found to enhance the proliferation, differentiation, and colony formation and restore the cytoskeletal morphology of primary keratinocytes in naturally aging skin in vitro. Furthermore, the anti-aging properties of CASIN on primary fibroblasts in aging mice were mediated by the ribosomal protein RPL4 using proteomic sequencing, influencing collagen synthesis and cytoskeletal morphology both in vitro and in vivo. Meanwhile, both subcutaneous injection and topical application exhibited anti-aging effects for a duration of 21 days. Additionally, CASIN exhibited anti-inflammatory properties, while reduced expression of RPL4 was associated with increased inflammation in the skin of naturally aging mice. Taken together, our results unveil a novel function of RPL4 in skin aging, providing a foundational basis for future investigations into ribosomal proteins. And CASIN shows promise as a potential anti-aging agent for naturally aging mouse skin, suggesting potential applications in the field., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Objectives: This study investigated the potential therapeutic benefits of PNU120596, a positive allosteric modulator of the α7 nicotinic acetylcholine receptor (α7nAChR), in mitigating acute lung injury (ALI) induced by lipopolysaccharide (LPS) in a mouse model. Specifically, we sought to examine the impact of PNU120596 on the PI3K/AKT signaling pathway in the context of ALI., Methods: ALI was induced in mice by LPS administration, and the protective effects of PNU120596 were assessed. Lung injury, lung function, and the inflammatory response were evaluated. Additionally, the activation of the PI3K/AKT signaling pathway was examined, along with the levels of inflammatory factors and oxidative stress markers., Key Findings: PNU120596 significantly ameliorated LPS-induced lung injury, improved lung function, and reduced the inflammatory response in the mouse model of ALI. Furthermore, we observed that PNU120596 inhibited the activation of the PI3K/AKT signaling pathway, which was associated with decreased levels of inflammatory factors and oxidative stress markers., Conclusions: PNU120596 exhibits promising therapeutic potential for the treatment of acute lung injury, potentially by targeting the PI3K/AKT signaling pathway. These findings suggest that modulation of the α7 nicotinic acetylcholine receptor with PNU120596 may offer a viable strategy for the management of ALI, warranting further investigation and potential clinical applications., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. 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.)

Background: Hematopoietic stem progenitor cells (HSPCs) undergo phenotypical and functional changes during their emergence and development. Although the molecular programs governing the development of human hematopoietic stem cells (HSCs) have been investigated broadly, the relationships between dynamic metabolic alterations and their functions remain poorly characterized., Methods: In this study, we comprehensively described the proteomics of HSPCs in the human fetal liver (FL), umbilical cord blood (UCB), and adult bone marrow (aBM). The metabolic state of human HSPCs was assessed via a Seahorse assay, RT‒PCR, and flow cytometry-based metabolic-related analysis. To investigate whether perturbing glutathione metabolism affects reactive oxygen species (ROS) production, the metabolic state, and the expansion of human HSPCs, HSPCs were treated with buthionine sulfoximine (BSO), an inhibitor of glutathione synthetase, and N-acetyl-L-cysteine (NAC)., Results: We investigated the metabolomic landscape of human HSPCs from the fetal, perinatal, and adult developmental stages by in-depth quantitative proteomics and predicted a metabolic switch from the oxidative state to the glycolytic state during human HSPC development. Seahorse assays, mitochondrial activity, ROS level, glucose uptake, and protein synthesis rate analysis supported our findings. In addition, immune-related pathways and antigen presentation were upregulated in UCB or aBM HSPCs, indicating their functional maturation upon development. Glutathione-related metabolic perturbations resulted in distinct responses in human HSPCs and progenitors. Furthermore, the molecular and immunophenotypic differences between human HSPCs at different developmental stages were revealed at the protein level for the first time., Conclusion: The metabolic landscape of human HSPCs at three developmental stages (FL, UCB, and aBM), combined with proteomics and functional validations, substantially extends our understanding of HSC metabolic regulation. These findings provide valuable resources for understanding human HSC function and development during fetal and adult life., (© 2024. The Author(s).)

Direct synthesis of graphene on nonmetallic substrates via chemical vapor deposition (CVD) has become a frontier research realm targeting transfer-free applications of CVD graphene. However, the stable mass production of graphene with a favorable growth rate and quality remains a grand challenge. Herein, graphene glass fiber fabric (GGFF) was successfully developed through the controllable growth of graphene on non-catalytic glass fiber fabric, employing a synergistic binary-precursor CVD strategy to alleviate the dilemma between growth rate and quality. The binary precursors consisted of acetylene and acetone, where acetylene with high decomposition efficiency fed rapid graphene growth while oxygen-containing acetone was adopted for improving the layer uniformity and quality. Notably, the bifurcating introducing-confluent premixing (BI-CP) system was self-built for the controllable introduction of gas and liquid precursors, enabling the stable production of GGFF. GGFF features solar absorption and infrared emission properties, based on which the self-adaptive dual-mode thermal management film was developed. This film can automatically switch between heating and cooling modes by spontaneously perceiving the temperature, achieving excellent thermal management performances with heating and cooling power of ∼501.2 and ∼108.6 W m -2 , respectively. These findings unlock a new strategy for the large-scale batch production of graphene materials and inspire advanced possibilities for further applications., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

Polysaccharides and various secondary metabolites are the major bioactive ingredients in Bletilla striata tubers and their biosynthesis and accumulation are influenced by light intensity. However, the mechanisms underlying shading effects remain largely unknown. In the present study, we used a combined analysis of the physiology, metabolome, and transcriptome to investigate the physiological activities and bioactive component accumulation of B. striata under different shading treatments (S0, S50, S70, and S90). The dry weight of shoots and tubers, net photosynthetic rate, and polysaccharide content were highest in S50 and lowest in S90. The content of precursors (sucrose, Glucose-6P, and Mannose-6P) for polysaccharide synthesis significantly increased in S50. However, the expression levels of genes involved in starch biosynthesis decreased in S50. Several structural genes involved in secondary metabolism, including cinnamic acid 4-hydroxylase (C4H), chalcone synthase (CHS), and 1-Deoxy-D-xylulose-5-phosphate synthase (DXS), showed decreased expression in S50. However, the shading effect on the biosynthesis of secondary metabolites (phenylpropanoids, flavonoids, and terpenoids) was inconsistent. Our study provides the molecular mechanisms underlying the effects of shading on the biosynthesis of polysaccharides and secondary metabolites in B. striata and offers a theoretical basis for the artificial cultivation and industrial production of bioactive ingredients., 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. The authors declare no conflict interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The use of programmed death-1 blockade has a significant therapeutic effect in patients with Mismatch Repair-Deficient/Microsatellite Instability-High metastatic colorectal cancer. However, data on preoperative single-agent programmed death-1 blockade are rare., Objective: This study aims to evaluate the effectiveness and safety of preoperative programmed death-1 blockade as a conversion strategy in patients with locally advanced and resectable metastatic Mismatch Repair-Deficient/Microsatellite Instability-High colorectal cancer., Design: This is a retrospective observational study., Settings: This study was conducted at a high-volume tertiary referral cancer center in China., Patients: Twenty-four patients of consecutive cases since 2020-2022 with Mismatch Repair-Deficient/Microsatellite Instability-High colorectal cancer who received preoperative single-agent programmed death-1 blockade were retrospectively reviewed. These patients had either bulking tumor scheduled for multivisceral resection, a strong desire for organ preservation, or potentially resectable metastatic lesions., Main Outcome Measures: Pathological complete response, clinical complete response, toxicity, R0 resection rate, and complications were evaluated., Results: Patients tolerated preoperative immunotherapy well. The R0 resection rate was 95.2% and the pathological complete response rate was 47.6%. Three patients (12.5%) were evaluated as clinical complete response and then underwent "watch and wait". One half of the cT4b patients were spared multivisceral resection, while 60% (3/5) achieved pathological complete response. All three patients with liver metastases obtained CR of all liver lesions after programmed death-1 blockade treatment. Grade III postoperative complications occurred in two patients., Limitations: The limitations of this study are as follows: retrospective study, small sample size, and short follow-up., Conclusions: Preoperative anti-programmed death-1 therapy alone as a conversion strategy in initially resected difficult dMMR/MSI-H colorectal cancer can achieve a high tumor complete response. The use of immuno-preoperative therapy in patients with T4b colon cancer or low rectal cancer can reduce multivisceral resection and achieve high organ function preservation. See Video Abstract., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Colon and Rectal Surgeons.)

Graphene chemical vapor deposition (CVD) growth directly on target using substrates presents a significant route toward graphene applications. However, the substrates are usually catalytic-inert and special-shaped; thus, large-scale, high-uniformity, and high-quality graphene growth is challenging. Herein, graphene-skinned glass fiber fabric (GGFF) was developed through graphene CVD growth on glass fiber fabric, a Widely used engineering material. A fluid dynamics rectification strategy was first proposed to synergistically regulate the distribution of carbon species in 3D space and their collisions with hierarchical-structured substrates, through which highly uniform deposition of high-quality graphene on fibers in large-scale 3D-woven fabric was realized. This strategy is universal and applicable to CVD systems using various carbon precursors. GGFF exhibits high electrical conductivity and photothermal conversion capability, based on which a natural energy harvester was first developed. It can harvest both solar and raindrop energy through solar heating and droplet-based electricity generating, presenting promising potentials to alleviate energy burdens.

Background: Previous studies have highlighted the catalytic activity of Escherichia coli alcohol dehydrogenase YahK in the presence of coenzyme nicotinamide adenine dinucleotide (NAD) and metal zinc. Notably, competitive interaction between iron and zinc ligands has been shown to influence the catalytic efficiency of several key proteases. This study aims to unravel the intricate mechanisms underlying YahK's catalytic action, with a particular focus on the pivotal roles played by metal ions zinc and iron., Methods: The purified YahK protein from E. coli cells cultivated in LB medium was utilized to investigate its metal-binding properties through UV-visible absorption measurements and determination of metal content. Subsequently, the effects of excess zinc and iron on the metal-binding ability and alcohol dehydrogenase activity of the YahK protein were explored using M9 minimal medium. Furthermore, site-directed mutagenesis technology was employed to determine the iron-binding site location within the YahK protein. Polyacrylamide gel electrophoresis was conducted to examine the relationship between iron and zinc with respect to the YahK protein., Results: The study confirmed the presence of iron and zinc in the YahK protein, with the zinc-bound form exhibiting enhanced catalytic activity in alcohol dehydrogenation reactions. Conversely, the presence of iron appears to play a pivotal role in maintaining overall stability of the YahK protein. Furthermore, experimental findings indicate that excessive zinc within M9 minimal medium can competitively bind to iron-binding sites on YahK, thereby augmenting its alcohol dehydrogenase activity., Conclusion: The dynamic binding of YahK to iron and zinc unveils its intricate regulatory mechanism as an alcohol dehydrogenase, thereby highlighting the possible physiological role of YahK in E. coli and its significance in governing cellular metabolic processes. This discovery provides a novel perspective for further investigating the specific impact of metal ion binding on YahK and E. coli cell metabolism., Competing Interests: The authors declare that they have no competing interests., (© 2024 Liang et al.)

With the acceleration of population aging, disability in older adults is a growing public health problem; however, little is known about the role of specific leisure-time activities in affecting disability. This study prospectively examined the association of leisure-time activities with disability among the Chinese oldest old. A total of 14 039 adults aged 80 years or older (median age of 89.8 years) were enrolled from the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2014. Disability was defined as the presence of concurrent impairment in activities of daily living and physical performance. Cox proportional hazards models were used to estimate the associations between leisure-time activities and disability. During a mean of 4.2 years (2.7 years) of follow-up, 4487 participants developed disability. Compared with participants who never engaged in leisure-time activities, participants who engaged in almost daily activities, including gardening, keeping domestic animals or pets, playing cards or mahjong, reading books or newspapers, and watching TV or listening to the radio had a lower risk of disability, with HRs of 0.78 (0.69-0.88), 0.64 (0.58-0.70), 0.74 (0.63-0.86), 0.74 (0.65-0.84), and 0.84 (0.77-0.90), respectively. Moreover, the risk of disability gradually decreased with participation in an increasing number of those leisure-time activities (P for trend <0.001). Frequent engagement in leisure-time activities was associated with a lower risk of disability among the Chinese oldest old. This study highlights the importance of incorporating a broad range of leisure-time activities into the daily lives of older adults., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

The utilization of metabolomics approaches to explore the metabolic mechanisms underlying plant fitness and adaptation to dynamic environments is growing, highlighting the need for an efficient and user-friendly toolkit tailored for analyzing the extensive datasets generated by metabolomics studies. Current protocols for metabolome data analysis often struggle with handling large-scale datasets or require programming skills. To address this, we present MetMiner (https://github.com/ShawnWx2019/MetMiner), a user-friendly, full-functionality pipeline specifically designed for plant metabolomics data analysis. Built on R shiny, MetMiner can be deployed on servers to utilize additional computational resources for processing large-scale datasets. MetMiner ensures transparency, traceability, and reproducibility throughout the analytical process. Its intuitive interface provides robust data interaction and graphical capabilities, enabling users without prior programming skills to engage deeply in data analysis. Additionally, we constructed and integrated a plant-specific mass spectrometry database into the MetMiner pipeline to optimize metabolite annotation. We have also developed MDAtoolkits, which include a complete set of tools for statistical analysis, metabolite classification, and enrichment analysis, to facilitate the mining of biological meaning from the datasets. Moreover, we propose an iterative weighted gene co-expression network analysis strategy for efficient biomarker metabolite screening in large-scale metabolomics data mining. In two case studies, we validated MetMiner's efficiency in data mining and robustness in metabolite annotation. Together, the MetMiner pipeline represents a promising solution for plant metabolomics analysis, providing a valuable tool for the scientific community to use with ease., (© 2024 The Author(s). Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

Various prenylated indoline alkaloids with diverse biological activities, including (-)-debromoflustramine B with significant butyrylcholinesterase inhibitory activity, could be synthesized by dearomative prenylation reactions of tryptophan derivatives. However, previously reported dearomative prenylations were limited to batch reactions at the milligram scale, requiring multistep reactions and complex post-processing to obtain the desired natural products. The more efficient synthesis of alkaloids remains challenging, as does the recovery of expensive catalysts. Herein, we developed a chiral heterogeneous Pd nanoparticle (NP) catalyst supported on a polymer, which produces indoline alkaloids in high yields with excellent enantioselectivities. Additionally, the first gram-scale four-step continuous-flow total synthesis of (-)-debromoflustramine B was successfully achieved with this chiral Pd heterogeneous catalyst, requiring only a simple post-processing step., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: To objectively quantify posterior capsule opacification (PCO) using swept-source anterior segment optical coherence tomography (SS-ASOCT) in pseudophakic eyes., Setting: Zhongshan Ophthalmic Center, Guangzhou, China., Design: Prospective cross-sectional study., Methods: One hundred and eighty eyes with PCO (37 multifocal intraocular lenses [MfIOLs] and 143 monofocal intraocular lenses [MoIOLs]) were enrolled. The PCO Irregular Degree (PID), defined to evaluate the surface irregularity of PCO, the average and maximum thickness of PCO (AT-PCO, MT-PCO) were applied to quantify PCO based on SS-ASOCT (CASIA2) images. Corrected distance visual acuity (CDVA), high order aberrations (HOAs), modulation transfer function (MTF) and Strehl ratio were recorded. The associations between SS-ASOCT parameters and visual function parameters were assessed by Spearman's correlation analysis., Results: PID, AT-PCO and MT-PCO showed significant correlations with CDVA, Strehl ratio and HOAs (CDVA: r = 0.702, 0.741, 0.736; Strehl ratio: r = -0.746, -0.719, -0.740; HOAs: r = 0.762, 0.734, 0.752). The correlations of these three parameters with Strehl ratio and HOAs were significantly higher than those of clinical PCO grading with Strehl ratio and HOAs (all P < 0.05). Particularly, PID demonstrated notable correlations with Strehl ratio and HOAs. In addition, patients with MfIOLs presented worse Strehl ratio and HOAs than those with MoIOLs after matching age, PID, AT-PCO and MT-PCO., Conclusions: This study provides a novel method for objectively quantifying PCO using successive cross-sectional SS-ASOCT images. AT-PCO, MT-PCO and PID are presented as new indicators to document PCO severity, with PID offering a unique perspective by considering the irregularity aspect of PCO., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Inappropriate homology-directed repair (HDR) of telomeres results in catastrophic telomere loss and aberrant chromosome fusions, leading to genome instability. We have previously shown that the TRF2-RAP1 heterodimer protects telomeres from engaging in aberrant telomere HDR. Cells lacking the basic domain of TRF2 and functional RAP1 display HDR-mediated telomere clustering, resulting in the formation of ultrabright telomeres (UTs) and massive chromosome fusions. Using purified proteins, we uncover three distinct molecular pathways that the TRF2-RAP1 heterodimer utilizes to protect telomeres from engaging in aberrant HDR. We show mechanistically that TRF2-RAP1 inhibits RAD51-initiated telomeric D-loop formation. Both the TRF2 basic domain and RAP1-binding to TRF2 are required to block RAD51-mediated homology search. TRF2 recruits the BLM helicase to telomeres through its TRFH domain to promote BLM-mediated unwinding of telomere D-loops. In addition, TRF2-RAP1 inhibits BLM-DNA2-mediated 5' telomere end resection, preventing the generation of 3' single-stranded telomere overhangs necessary for RAD51-dependent HDR. Importantly, cells expressing BLM mutants unable to interact with TRF2 accumulate telomere D-loops and UTs. Our findings uncover distinct molecular mechanisms coordinated by TRF2-RAP1 to protect telomeres from engaging in aberrant HDR., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Cryptococcal meningitis (CM) is a well-recognized fungal infection, with substantial mortality in individuals infected with the human immunodeficiency virus (HIV). However, the incidence, risk factors, and outcomes in non-HIV adults remain poorly understood. This study aims to investigate the characteristics and prognostic indicators of CM in non-HIV adult patients, integrating a novel predictive model to guide clinical decision-making. A retrospective cohort of 64 non-HIV adult CM patients, including 51 patients from previous studies and 13 from the First Hospital of Shanxi Medical University, was analyzed. We assessed demographic features, underlying diseases, intracranial pressure, cerebrospinal fluid characteristics, and brain imaging. Using the least absolute shrinkage and selection operator (LASSO) method, and multivariate logistic regression, we identified significant variables and constructed a Nomogram prediction model. The model's calibration, discrimination, and clinical value were evaluated using the Bootstrap method, calibration curve, C index, goodness-of-fit test, receiver operating characteristic (ROC) analysis, and decision curve analysis. Age, brain imaging showing parenchymal involvement, meningeal and ventricular involvement, and previous use of immunosuppressive agents were identified as significant variables. The Nomogram prediction model displayed satisfactory performance with an akaike information criterion (AIC) value of 72.326, C index of 0.723 (0.592-0.854), and area under the curve (AUC) of 0.723, goodness-of-fit test P = 0.995. This study summarizes the clinical and imaging features of adult non-HIV CM and introduces a tailored Nomogram prediction model to aid in patient management. The identification of predictive factors and the development of the nomogram enhance our understanding and capacity to treat this patient population. The insights derived have potential clinical implications, contributing to personalized care and improved patient outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Objectives: This meta-analysis aimed to explore the relationship between the dose of acupuncture sessions, acupuncture frequency, and acupuncture duration and its effects on migraine., Methods: Eight databases were searched for randomized controlled trials (RCTs) evaluating the efficacy of penetrating manual acupuncture for migraine published in English and Chinese from inception to June 20, 2024. The robust-error meta-regression (REMR) approach and non-linear meta-regression with restricted cubic spline (RCS) were used to investigate the dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and the frequency of migraine attacks. The potential nonlinear relationships was tested by restricting the regression coefficient to zero and a P value＜0.1. The statistical analysis was conducted using Stata 17.0. The risk of bias was independently assessed by two reviewers using the Cochrane tool. The reporting quality for acupuncture procedures was evaluated by STRICTA criteria., Results: Thirty-two RCTs involving 1562 participants were included, and the results showed a J-shaped dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. After 16 acupuncture sessions, the change in the frequency of migraine attacks was 3.95 (95 %CI: 3.13 to 4.77). Three sessions of acupuncture a week resulted in a significant decrease in the frequency of migraine attacks, reaching 4.04 (95 % CI: 2.49 to 5.58). After two months of acupuncture, the frequency of migraine attacks decreased significantly, showing a difference of 4.05 (95 % CI: 3.61 to 4.49). Subsequently, the improvement trend gradually flattened, yielding diminishing benefits to patients. The risk of bias showed that seven studies were rated as "low risk", two were rated as "high risk", and the others were rated as "unclear risk". The reporting quality of RCTs of acupuncture for migraine remain suboptimal., Conclusions: A non-linear dose-response relationship was found between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. The results of our study recommend 16 sessions of acupuncture with a frequency of 3 sessions/week and a treatment duration of 1.5 to 2 months., Registration Number: This meta-analysis has been registered on PROSPERO (CRD42023400493)., Competing Interests: Declaration of Competing Interest The author reports no conflicts of interest in this work., (Copyright © 2024. Published by Elsevier Ltd.)

Hematopoietic stem progenitor cells (HSPCs) give rise to the hematopoietic system, maintain hematopoiesis throughout the lifespan, and undergo molecular and functional changes during their development and aging. The importance of hematopoietic stem cell (HSC) biology has led to their extensive characterization at genomic and transcriptomic levels. However, the proteomics of HSPCs throughout the murine lifetime still needs to be fully completed. Here, using mass spectrometry (MS)-based quantitative proteomics, we report on the dynamic changes in the proteome of HSPCs from four developmental stages in the fetal liver (FL) and the bone marrow (BM), including E14.5, young (2 months), middle-aged (8 months), and aging (18 months) stages. Proteomics unveils highly dynamic protein kinetics during the development and aging of HSPCs. Our data identify stage-specific developmental features of HSPCs, which can be linked to their functional maturation and senescence. Our proteomic data demonstrated that FL HSPCs depend on aerobic respiration to meet their proliferation and oxygen supply demand, while adult HSPCs prefer glycolysis to preserve the HSC pool. By functional assays, we validated the decreased mitochondrial metabolism, glucose uptake, reactive oxygen species (ROS) production, protein synthesis rate, and increased glutathione S-transferase (GST) activity during HSPC development from fetal to adult. Distinct metabolism pathways and immune-related pathways enriched in different HSPC developmental stages were revealed at the protein level. Our study will have broader implications for understanding the mechanism of stem cell maintenance and fate determination and reversing the HSC aging process., 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.)

Bone metastasis (BM) is a mortality-related event of late-stage cancer, with non-small cell lung cancer (NSCLC) being a common origin for BM. However, the detailed molecular profiling of the metastatic bone ecosystem is not fully understood, hindering the development of effective therapies for advanced patients. In this study, we examined the cellular heterogeneity between primary tumours and BM from tissues and peripheral blood by single-cell transcriptomic analysis, which was verified using multiplex immunofluorescence staining and public datasets. Our results demonstrate a senescent microenvironment in BM tissues of NSCLC. BM has a significantly higher infiltration of malignant cells with senescent characteristics relative to primary tumours, accompanied by aggravated metastatic properties. The endothelial-mesenchymal transition involved with SOX18 activation is related to the cellular senescence of vascular endothelial cells from BM. CD4Tstr cells, with pronounced stress and senescence states, are preferentially infiltrated in BM, indicating stress-related dysfunction contributing to the immunocompromised environment during tumour metastasis to bone. Moreover, we identify the SPP1 pathway-induced cellular crosstalk among T cells, vascular ECs and malignant cells in BM, which activates SOX18 and deteriorates patient survival. Our findings highlight the roles of cellular senescence in modulating the microenvironment of BM and implicate anti-senescence therapy for advanced NSCLC patients., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Non-alcoholic fatty liver disease (NAFLD), a metabolic-associated fatty liver disease, has become the most common chronic liver disease worldwide. Recently, the discovery of cuproptosis, a newly identified mode of cell death, further highlighted the importance of copper in maintaining metabolic homeostasis. An increasing number of studies have confirmed that liver copper metabolism is closely related to the pathogenesis of NAFLD. However, the relationship between NAFLD and copper metabolism, especially cuproptosis, remains unclear. In this review, we aim to summarize the current understanding of copper metabolism and its dysregulation, particularly the role of copper metabolism dysregulation in the pathogenesis of NAFLD. More importantly, this review emphasizes potential gene-targeted therapeutic strategies, challenges and the future of cuproptosis-related genes in the treatment of NAFLD. This review aims to provide innovative therapeutic strategies for NAFLD., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)