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Genetically modified crops (GMCs) have been discussed due to unknown safety, and thus, it is imperative to develop an effective detection technology. CRISPR/Cas is deemed a burgeoning technology for nucleic acid detection. Herein, we developed a novel detection method for the first time, which combined thermostable Cas12b with loop-mediated isothermal amplification (LAMP), to detect genetically modified (GM) soybeans in a customized one-pot vessel. In our method, LAMP-specific primers were used to amplify the cauliflower mosaic virus 35S promoter (CaMV35S) of the GM soybean samples. The corresponding amplicons activated the trans -cleavage activity of Cas12b, which resulted in the change of fluorescence intensity. The proposed bioassay was capable of detecting synthetic plasmid DNA samples down to 10 copies/μL, and as few as 0.05% transgenic contents could be detected in less than 40 min. This work presented an original detection method for GMCs, which performed rapid, on-site, and deployable detection.

Objectives: This study investigates the relationships between childhood adversities and the provision of informal care for older parents in later life in China., Method: The data came from four waves of the China Health and Retirement Longitudinal Study (CHARLS, N = 20,047). Using multilevel logistic regression models, we examined the relationships between adverse experiences in childhood and both the propensity and intensity of caregiving for older parents. Drawing on the regression results, we then estimated the total number of caregivers for older parents in China., Results: Experiencing one additional childhood adversity was associated with a decrease of 8% in the odds of providing informal care (p<0.001). The association between childhood adversity and caregiving remained significant after socio-demographic factors and later life outcomes were controlled for. We estimated that 58.3 million middle-aged adults in China were providing care for parents in 2020. Had people experienced one fewer adversity in their childhood, there would have been 2.2 million more caregivers in 2020. Had they experienced two fewer adversities, there would have been 3.4 million more caregivers., Discussion: The factors associated with informal caregiving can be traced back to early life experiences. To address the shortage of informal care supply, it is crucial to foster a caring culture from the very beginning of human development., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Zinc oxide nanoparticles (ZnO NPs) cause biotoxicity and pose a potential ecological threat; however, their effects on plant metabolism and eco-corona evolution between NPs and organisms remain unclear. This study clarified the molecular mechanisms underlying physiological and metabolic responses induced by three different ZnO NPs with different sizes and hydrophobicity in sprouts ( Vigna radiata ) and explored the critical regulation of eco-corona formation in root-nano systems. Results indicated that smaller-sized ZnO inhibited root elongation by up to 37.14% and triggered oxidative burst and apoptosis. Metabolomics confirmed that physiological maintenance after n-ZnO exposure was mainly attributed to the effective stabilization of nitrogen fixation and defense systems by biotransformation of the flavonoid pathway. Larger-sized or hydrophobic group-modified ZnO exhibited low toxicity in sprouts, with 0.89-fold upregulation of citrate in central carbon metabolism. This contributed to providing energy for resistance to NP stress through amino acid and carbon/nitrogen metabolism, accompanied by changes in membrane properties. Notably, smaller-sized and hydrophobic NPs intensely stimulated the release of root metabolites, forming corona complexes with exudates. The hydrogen-bonded wrapping mechanism in protein secondary structure and hydrophobic interactions of heterogeneous functional groups drove eco-corona formation, along with the corona evolution intensity of n-ZnO > s-ZnO > b-ZnO based on higher (α-helix + 3-turn helix)/β-sheet ratios. This study provides crucial insight into metabolic and eco-corona evolution in bionano fates.

We report that constructed Au nanoclusters (NCs) can afford amazing white emission synergistically dictated by the Au(0)-dominated core-state fluorescence and Au(I)-governed surface-state phosphorescence, with record-high absolute quantum yields of 42.1% and 53.6% in the aqueous solution and powder state, respectively. Moreover, the dynamic color tuning is achieved in a wide warm-to-cold white-light range (with the correlated color temperature varied from 3426 to 24 973 K) by elaborately manipulating the ratio of Au(0) to Au(I) species and thus the electron transfer rate from staple motif to metal kernel. This study not only exemplifies the successful integration of multiple luminescent centers into metal NCs to accomplish efficient white-light emission but also inspires a feasible pathway toward customizing the optical properties of metal NCs by regulating electron transfer kinetics.

Background: The ability to generate functional hepatocytes without relying on donor liver organs holds significant therapeutic promise in the fields of regenerative medicine and potential liver disease treatments. Clustered regularly interspaced short palindromic repeats (CRISPR) activator (CRISPRa) is a powerful tool that can conveniently and efficiently activate the expression of multiple endogenous genes simultaneously, providing a new strategy for cell fate determination. The main purpose of this study is to explore the feasibility of applying CRISPRa for hepatocyte reprogramming and its application in the treatment of mouse liver fibrosis., Method: The differentiation of mouse embryonic fibroblasts (MEFs) into functional induced hepatocyte-like cells (iHeps) was achieved by utilizing the CRISPRa synergistic activation mediator (SAM) system, which drove the combined expression of three endogenous transcription factors-Gata4, Foxa3, and Hnf1a-or alternatively, the expression of two transcription factors, Gata4 and Foxa3. In vivo, we injected adeno-associated virus serotype 6 (AAV6) carrying the CRISPRa SAM system into liver fibrotic Col1a1-CreER; Cas9fl/fl mice, effectively activating the expression of endogenous Gata4 and Foxa3 in fibroblasts. The endogenous transcriptional activation of genes was confirmed using real-time quantitative polymerase chain reaction (RT-qPCR) and RNA-seq, and the morphology and characteristics of the induced hepatocytes were observed through microscopy. The level of hepatocyte reprogramming in vivo is detected by immunofluorescence staining, while the improvement of liver fibrosis is evaluated through Sirius red staining, alpha-smooth muscle actin (α-SMA) immunofluorescence staining, and blood alanine aminotransferase (ALT) examination., Results: Activation of only two factors, Gata4 and Foxa3, via CRISPRa was sufficient to successfully induce the transformation of MEFs into iHeps. These iHeps could be expanded in vitro and displayed functional characteristics similar to those of mature hepatocytes, such as drug metabolism and glycogen storage. Additionally, AAV6-based delivery of the CRISPRa SAM system effectively induced the hepatic reprogramming from fibroblasts in mice with live fibrosis. After 8 weeks of induction, the reprogrammed hepatocytes comprised 0.87% of the total hepatocyte population in the mice, significantly reducing liver fibrosis., Conclusion: CRISPRa-induced hepatocyte reprogramming may be a promising strategy for generating functional hepatocytes and treating liver fibrosis caused by hepatic diseases., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Perovskite light-emitting diodes (PeLEDs) based on CsPb(Br/I) 3 nanocrystals (NCs) usually suffer from severe spectral instability under operating voltage due to the poor-quality PeNCs. Herein, zeolite was utilized to prepare high-quality CsPb(Br/I) 3 NCs via promoting the homogeneous nucleation and growth and suppressing the Ostwald ripening of PeNCs. In addition, the decomposed zeolite interacted strongly with PeNCs through Pb-O bonds and hydrogen bonds, which inhibited the formation of defects and suppressed halide ion migration, leading to an improved photoluminescence quantum yield (PLQY) and enhanced stability of PeNCs. Moreover, the strong binding affinity of decomposed zeolite to PeNCs contributed to the formation of homogeneous perovskite films with high PLQY. As a result, pure-red PeLEDs with Commission International de I'Eclairage (CIE) coordinates of (0.705, 0.291) were fabricated, approaching the Rec. 2020 red primary color. The devices achieved a peak external quantum efficiency of 23.0% and outstanding spectral stability.

In contemporary studies, the predominant utilization of C 60 derivatives pertains to their role as photosensitizers or agents that scavenge free radicals. The intriguing coexistence of these divergent functionalities has prompted extensive investigation into water-soluble fullerenes. The photodynamic properties of these compounds find practical applications in DNA cleavage, antitumor interventions, and antibacterial endeavors. Consequently, photodynamic therapy is progressively emerging as a pivotal therapeutic modality within the biomedical domain, owing to its notable levels of safety and efficacy. The essential components of photodynamic therapy encompass light of the suitable wavelength, oxygen, and a photosensitizer, wherein the reactive oxygen species generated by the photosensitizer play a pivotal role in the therapeutic mechanism. The remarkable ability of fullerenes to generate singlet oxygen has garnered significant attention from scholars worldwide. Nevertheless, the limited permeability of fullerenes across cell membranes owing to their low water solubility necessitates their modification to enhance their efficacy and utilization. This paper reviews the applications of fullerene derivatives as photosensitizers in antitumor and antibacterial fields for the recent years., 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 Masson SAS. All rights reserved.)

The aging of microplastics (MPs) is extremely influenced by photochemically-produced reactive intermediates (PPRIs), which are mediated by natural photosensitive substances. Algal extracellular polymeric substances (EPS) can produce PPRIs when exposed to sunlight. Nonetheless, the specific role of EPS in the aging process of MPs remains unclear. This work systematically explored the aging process of polystyrene (PS) MPs in the EPS secreted by Chlorella vulgaris under simulated sunlight irradiation. The results revealed that the existence of EPS accelerated the degradation of PS MPs into particles with sizes less than 1 µm, while also facilitating the formation of hydroxy groups on the surface. The release rate of dissolved organic matter (DOM) from PS MPs was elevated from 0.120 mg·L -1 ·day -1 to 0.577 mg·L -1 ·day -1 . The primary factor contributing to the elevated levels of DOM was humic acid-like compounds generated through the breakdown of PS. EPS accelerated the aging process of PS MPs by primarily mediating the formation of triplet excited states ( 3 EPS*), singlet oxygen ( 1 O 2 ), and superoxide radicals (O 2 ∙- ), resulting in indirect degradation. 3 EPS* was found to have the most substantial impact. This study makes a significant contribution to advance understanding of the environmental fate of MPs in aquatic environments impacted by algal blooms., 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.)

Mucosal melanoma exhibits limited responsiveness to anti-PD-1 therapy. However, a subgroup of mucosal melanomas, particularly those situated at specific anatomical sites like primary malignant melanoma of the esophagus (PMME), display remarkable sensitivity to anti-PD-1 treatment. The underlying mechanisms driving this superior response and the DNA methylation patterns in mucosal melanoma have not been thoroughly investigated. We collected tumor samples from 50 mucosal melanoma patients, including 31 PMME and 19 non-esophageal mucosal melanoma (NEMM). Targeted bisulfite sequencing was conducted to characterize the DNA methylation landscape of mucosal melanoma and explore the epigenetic profiling differences between PMME and NEMM. Bulk RNA sequencing and multiplex immunofluorescence staining were performed to confirm the impact of methylation on gene expression and immune microenvironment. Our analysis revealed distinct epigenetic signatures that distinguish mucosal melanomas of different origins. Notably, PMME exhibited distinct epigenetic profiling characterized by a global hypermethylation alteration compared to NEMM. The prognostic model based on the methylation scores of a 7-DMR panel could effectively predict the overall survival of PMME patients and potentially serve as a prognostic factor. PMME displayed a substantial enrichment of immune-activating cells in contrast to NEMM. Furthermore, we observed hypermethylation of the TERT promoter in PMME, which correlated with heightened CD8+ T cell infiltration, and patients with hypermethylated TERT were likely to have improved responses to immunotherapy. Our results indicated that PMME shows a distinct methylation landscape compared with NEMM, and the epigenetic status of TERT might be used to estimate prognosis and direct anti-PD-1 treatment for mucosal melanoma.

Ischemic heart disease is caused by coronary artery occlusion. Despite the increasing number and success of interventions for restoring coronary artery perfusion, myocardial ischemia-reperfusion (I/R) injury remains a significant cause of morbidity and mortality worldwide. Inspired by the impact of I/R on the Cx43 trafficking to the intercalated discs (ICDs), we aim to explore the potential mechanisms underlying the downregulation of Cx43 in ICDs after myocardial I/R. Gene set enrichment analysis (GSEA), Western blotting, and immunofluorescence experiments showed that Myocardial I/R activated the P38MAPK signaling pathway and promoted microtubule depolymerization. Inhibition of P38MAPK signaling pathway activation attenuated I/R-induced microtubule depolymerization. The ability of SB203580 to recover the distribution of Cx43 and electrophysiological parameters in I/R myocardium depended on microtubule stability. Our study suggests that microtubule depolymerization caused by the activation of the P38MAPK signaling pathway is an important mechanism underlying the downregulation of Cx43 in ICDs after myocardial I/R., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Clinical manifestations of vitamin B12 deficiency are varied and may result in missed or delayed diagnosis. This investigation explores the diverse clinical manifestations and demographic characteristics of vitamin B12 deficiency in neurology outpatients, aiming to enhance timely diagnosis and outcomes., Methods: The severity of vitamin B12 deficiency was classified as absolute (≤150 pg/mL) or borderline deficiency (150-300 pg/mL). We conducted a retrospective analysis of 165 outpatients with vitamin B12 deficiency at the department of neurology between May 2020 and May 2021., Result: Absolute vitamin B12 deficiency was found in 23.0% of the patients. The most common age range was 50-60 years, the most common cause was vegetarianism, and the most common symptom was headache. Epileptiform symptoms were more likely to occur in younger patients (<20 years old) with vitamin B12 deficiency, whereas psychiatric symptoms were more likely to occur in older patients (>70 years old). Vegetarians, salivation, and nonmegaloblastic anemia were more obvious in patients with absolute vitamin B12 deficiency, whereas headaches often showed borderline B12 deficiency., Conclusions: The clinical characteristics of vitamin B12 deficiency are complex and nonspecific. The diagnosis should be based on multiple factors., Competing Interests: Conflicts of interest and source of funding: The authors have no conflicts of interest to declare. This work was supported by the National Natural Science Foundation of China (grant 82171456 and 81971229 to Qin Yang)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Lanthanide-based lead-free perovskite materials hold great promise for the development of high-resolution full-color displays in the future. Here, various Cs 3 LnCl 6 perovskite nanocrystals (NCs) emitting light across the visible to near-infrared spectrum with remarkably high photoluminescence quantum yield (PLQY) are systemically prepared. Especially, by introducing multifunctional coumarin small molecules into Cs 3 EuCl 6 NCs as an intermediate state, Cs 3 EuCl 6 NCs can achieve an impressive PLQY of 92.4% with pure red emission and an exceptional energy transfer efficiency of nearly 93.2%. Furthermore, the lanthanide-based electroluminescent devices in red, green, and blue are successfully fabricated. Among them, the Cs 3 EuCl 6 -NC-based red light-emitting diode (LED) demonstrates a FWHM of 18 nm at 617 nm, an external quantum efficiency up to 5.17%, and a maximum brightness of 2373 cd m -2 , which is the most excellent reported for lead-free narrowband (within 20 nm) emission devices. Notably, these devices exhibit an operating half-life of 440 h at a brightness level of 100 cd m -2 , surpassing the performance of most reported lead-free perovskite LEDs (PLEDs). This work opens up exciting possibilities for the future commercialization of lanthanide-based PLEDs in the display industry, paving the way for more vibrant, energy-efficient, and long-lasting display technologies., (© 2024 Wiley‐VCH GmbH.)

The incidence of digestive malignancies has increased in recent years, including colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pancreatic cancer. Advanced stages of these cancers are prone to metastasis, which seriously reduce the standard of living of patients and lead to decline in the survival rate of patients. So far there are no good specific drugs to stop this phenomenon. It is very important and urgent to find new biomarkers and therapeutic targets. Purinergic ligand-gated ion channel 7 receptor (P2X7R) is ATP-gated and nonselective ion channel receptor involved in many inflammatory processes and cancer progression. P2X7R is present in many cancer cells and promotes or inhibits cancer development through signal transduction. Studies have presented that P2X7R plays a role in the proliferation and migration of digestive system cancers, such as CRC, HCC and pancreatic cancer. Therefore, P2X7R may serve as a biomarker or therapeutic target for digestive system cancers. This paper describes the structure and function of P2X7R, and mainly reviews the research progress on the role of P2X7R in CRC, HCC and pancreatic cancer., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Dysbiosis of gut microbiota is believed to be associated with inflammatory bowel disease (IBD). Ginsenoside compound K (CK), the main metabolite of Panax ginseng ginsenoside, has proven effective as an anti-inflammatory agent in IBD. However, the mechanisms by which CK modulates gut microbiota to ameliorate IBD remain poorly understood. Herein, CK demonstrated the potential to suppress the release of proinflammatory cytokines by gut microbiota modulation. Notably, supplementation with CK promoted the restoration of a harmonious balance in gut microbiota, primarily by enhancing the populations of Lactobacillus and Akkermansia . Furthermore, CK considerably elevated the concentrations of tryptophan metabolites derived from Lactobacillus that could activate the aryl hydrocarbon receptor. Overall, the promising alleviative efficacy of CK primarily stemmed from the promotion of Lactobacillus growth and production of tryptophan metabolites, suggesting that CK should be regarded as a prospective prebiotic agent for IBD in the future.

Background: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically., Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated., Results: Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1β, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway., Conclusion: Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research., Competing Interests: The authors declared that they have no conflicts of interest in this work., (© 2024 Zhang et al.)

Purpose: There has been limited evidence for the association between pulse pressure (PP) and proteinuria in prediabetes. The aim of our study was to explore the association between PP and albuminuria in community-dwelling Chinese adults with prediabetes. Materials and Methods: PP and urinary albumin-to-creatinine ratio (ACR) were measured in 2012 prediabetic patients and 3596 control subjects with normal glucose tolerance. Multivariate logistic regression models were used to evaluate the possible association of PP with the risk of presence of albuminuria. Results: PP was positively associated with the presence of albuminuria, and subjects in the higher PP quartiles had higher urinary ACR and presence of albuminuria as compared with those in the lowest quartile in both prediabetes and control groups (all P  < 0.01). Multivariate logistic regression analysis demonstrated that the highest PP quartile was positively associated with increased risk of presence of albuminuria in all prediabetic subjects [odds ratio (OR): 2.289, 95% confidence interval (CI) 1.364-3.842, P  < 0.01) and prediabetic subjects without anti-hypertensive drugs (OR: 1.932, 95% CI 1.116-3.343, P  < 0.01), whereas higher PP quartile has nothing to do with the risk of presence of albuminuria in control subjects with and without anti-hypertensive drugs after adjustment for potential confounders (all P  > 0.01). Consistently, stratified analysis showed that in the prediabetes group, the risks of presence of albuminuria progressively elevated with increasing PP quartiles in men, those aged 60 years or older, and with overweight/obesity, normal high-density lipoprotein cholesterol, and appropriate low-density lipoprotein cholesterol (all P for trend <0.05). Conclusion: Higher PP is independently related to increased risk of presence of albuminuria in community-dwelling Chinese adults with prediabetes.

Photocatalytic reduction of U(VI) is a promising method for removing uranium containing pollutants. However, using polyoxometalate-based metal-organic frameworks (POMOFs) for photoreduction of U(VI) is rare, and the relevant charge transfer pathway is also not yet clear. In this article, we demonstrate a highly efficient strategy and revealed a clearly electron transfer pathway for the photoreduction of U(VI) with 99% removal efficiency by using a novel POMOF, [Cu(4,4'-bipy)] 5 ·{AsMo 4 V Mo 6 VI V 2 V O 40 (V IV O)[V IV O(H 2 O)]}·2H 2 O ( 1 ), as catalyst. The POMOF catalyst was constructed by the connection of reduced {AsMo 10 V 4 } clusters and Cu(I)-MOF chains through Cu-O coordination bonds, which exhibits a broader and stronger light absorption capacity due to the presence of reduced {AsMo 10 V 4 } clusters. Significantly, the transition of electrons from Cu(I)-MOF to {AsMo 10 V 4 } clusters (Cu → Mo/V) greatly inhibits the recombination of photogenerated carriers, thereby advancing electron transfer. More importantly, the {AsMo 10 V 4 } clusters are not only adsorption sites but also catalytically active sites. This causes the fast transfer of photogenerated electrons from Mo/V to UO 2 2+ (Mo/V → O → U) via the surface oxygen atoms. The shorter electron transmission distance between catalytic active sites and UO 2 2+ achieves faster and more effective electron transport. All in all, the highly effective photocatalytic removal of U(VI) using the POMOF as a catalyst is predominantly due to the synergistic interaction between Cu(I)-MOFs and reduced {AsMo 10 V 4 } clusters.

Lysine lactylation (Kla) links metabolism and gene regulation and plays a key role in multiple biological processes. However, the regulatory mechanism and functional consequence of Kla remain to be explored. Here, we report that HBO1 functions as a lysine lactyltransferase to regulate transcription. We show that HBO1 catalyzes the addition of Kla in vitro and intracellularly, and E508 is a key site for the lactyltransferase activity of HBO1. Quantitative proteomic analysis further reveals 95 endogenous Kla sites targeted by HBO1, with the majority located on histones. Using site-specific antibodies, we find that HBO1 may preferentially catalyze histone H3K9la and scaffold proteins including JADE1 and BRPF2 can promote the enzymatic activity for histone Kla. Notably, CUT&Tag assays demonstrate that HBO1 is required for histone H3K9la on transcription start sites (TSSs). Besides, the regulated Kla can promote key signaling pathways and tumorigenesis, which is further supported by evaluating the malignant behaviors of HBO1- knockout (KO) tumor cells, as well as the level of histone H3K9la in clinical tissues. Our study reveals HBO1 serves as a lactyltransferase to mediate a histone Kla-dependent gene transcription., (© 2024. The Author(s).)

Objective: his study aimed to systematically evaluate the clinical efficacy of gabapentin and pregabalin in the treatment of acute herpes zoster neuralgia, including pain control and the occurrence of adverse effects., Method: A systematic computerized search was conducted in October 2023 in PubMed, Embase, Web of Science, Cochrane Library, VIP, CNKI, and Wanfang databases. Data from randomized controlled trials comparing gabapentin analogs for the treatment of acute herpes zoster neuralgia were searched. Endpoints were visual analog scores (VAS) and adverse effects at 1, 2, and 4 weeks. Data from studies that met the inclusion criteria were extracted for meta-analysis and sensitivity analysis using Revman 5.4 and Stata16., Results: The study included 292 patients from 6 RCTs. Of these, 118 were in the gabapentin-treated group, 37 were in the pregabalin-treated group, and 137 were in the placebo-controlled group. The gabapentin group showed superior pain reduction compared to the placebo group (P<0.05), but adverse events were more frequent., Conclusion: Gabapentin can effectively reduce acute herpes zoster neuralgia in patients. Pregabalin requires additional randomized controlled trials to supplement the analysis., Prospero Registration: CRD42023446643., Competing Interests: Declaration of Conflicting Interests: The authors declared that there is no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Two polyoxometalate-based hybrids, [M(btap) 3 (H 2 O) 3 (HPW 12 O 40 )]· x H 2 O (M-PW, M = Co/Mn, btap = 3,5-bis(1',2',4'-triazol-1'-yl)pyridine) were synthesized. Co-PW exhibited higher activity and selectivity towards olefin epoxidation than Mn-PW due to the synergistic effect between Co II and PW, in which the Co centers activate O 2 to ˙O 2 - and further binding of free H + from PW affords the active peroxyacid.

The pervasive use of smartphones, while enhancing accessibility to information and communication, has raised concerns about its potential negative effects on physical and mental health, including the impairment of decision-making abilities. This study investigates the influence of smartphone addiction on decision-making in college students. A sample of 80 individuals aged 17 to 26 was selected and divided into two groups based on their Smartphone Addiction Scale-Short Version (SAS-SV) scores. Participants underwent the Iowa Gambling Task (IGT) to evaluate their decision-making in risky and uncertain conditions, while fNIRS recorded their prefrontal cortex activity. The study found that individuals prone to smartphone addiction tend to make riskier choices in risky situations. However, when faced with decisions based on ambiguity, the smartphone addiction group showed increased brain activity in the dlPFC (specifically in channels 4, 9, and 11) compared to when making risky decisions. Despite this increased brain activation, there was no observable difference in behavior between the addiction-prone and control groups in ambiguous scenarios. Notably, the left dlPFC (e.g., channel 4) exhibited significantly higher activation in the addiction group compared to the control group. Findings suggest that smartphone addiction can detrimentally influence decision-making, behaviorally and neurologically, particularly in uncertain contexts. This study supports the classification of smartphone addiction as a genuine addiction and underscores its significance in psychiatric research. In essence, our research underscores the adverse effects of excessive smartphone use on decision-making processes, reinforcing the necessity to treat smartphone addiction as a pressing public health issue., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Tian, Bai, Liu, Li, Zhou and Lei.)

Objective: The aim of this study was to disseminate insights from a nationwide pilot of the International Classification of Diseases-11th revision (ICD-11)., Materials and Methods: The strategies and methodologies employed to implement the ICD-11 morbidity coding in 59 hospitals in China are described. The key considerations for the ICD-11 implementation were summarized based on feedback obtained from the pilot hospitals. Coding accuracy and Krippendorff's alpha reliability were computed based on the coding results in the ICD-11 exam., Results: Among the 59 pilot hospitals, 58 integrated ICD-11 Coding Software into their health information management systems and 56 implemented the ICD-11 in morbidity coding, resulting in 3 723 959 diagnoses for 873 425 patients being coded over a 2-month pilot coding phase. The key considerations in the transition to the ICD-11 in morbidity coding encompassed the enrichment of ICD-11 content, refinement of tools, provision of systematic and tailored training, improvement of clinical documentation, promotion of downstream data utilization, and the establishment of a national process and mechanism for implementation. The overall coding accuracy was 82.9% when considering the entire coding field (including postcoordination) and 92.2% when only one stem code was considered. Krippendorff's alpha was 0.792 (95% CI, 0.788-0.796) and 0.799 (95% CI, 0.795-0.803) with and without consideration of the code sequence, respectively., Conclusion: This nationwide pilot study has enhanced national technical readiness for the ICD-11 implementation in morbidity, elucidating key factors warranting careful consideration in future endeavors. The good accuracy and intercoder reliability of the ICD-11 coding achieved following a brief training program underscore the potential for the ICD-11 to reduce training costs and provide high-quality health data. Experiences and lessons learned from this study have contributed to WHO's work on the ICD-11 and can inform other countries when formulating their transition plan., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Miltiradiene serves as a crucial precursor in the synthesis of various high-value abietane-type diterpenes, exhibiting diverse pharmacological activities. Previous efforts to enhance miltiradiene production have primarily focused on the mevalonate acetate (MVA) pathway. However, limited emphasis has been placed on optimizing the supply of acetyl-CoA and NADPH. In this study, we constructed a platform yeast strain for miltiradiene production by reinforcing the biosynthetic pathway of geranylgeranyl diphosphate (GGPP) and acetyl-CoA, and addressing the imbalance between the supply and demand of the redox cofactor NADPH within the cytoplasm, resulting in an increase in miltiradiene yield to 1.31 g/L. Furthermore, we conducted modifications to the miltiradiene synthase fusion protein t Sm KSL1- Cf TPS1. Finally, the comprehensive engineering strategies and protein modification strategies culminated in 1.43 g/L miltiradiene in the engineered yeast under shake flask culture conditions. Overall, our work established efficient yeast cell factories for miltiradiene production, providing a foothold for heterologous biosynthesis of abietane-type diterpenes.

The current Radiotherapy (RT) technology still inevitably irradiated normal brain tissue, causing implicit radiation-induced injury. This study investigates the precise localization and the corresponding radiation dosage of brain regions susceptible to damage in nasopharyngeal carcinoma (NPC) patients following RT. Utilizing the Advanced Normalization Tools (ANTs) package, a computed tomography (CT) brain template was created in the standard Montreal Neurological Institute (MNI) space, based on 803 Chinese NPC patients (T0~T4) who underwent RT. With this template, all patients' CT and RTdose data were registered to the MNI space, and the RTdose distribution characteristics in normal brain tissues were compared for NPC patients treated with Intensity-modulated radiotherapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT), with patients' age and gender as covariates. Analysis of the average dosages indicated that certain areas within the Limbic, Temporal, and Posterior Lobes, the Brainstem, and the Cerebellum Posterior Lobe were exposed to doses exceeding 50 Gy. Inter-group analysis revealed that IMRT delivered higher doses than VMAT to brain regions anterior to the nasopharyngeal tumor, whereas VMAT affected the posterior regions more. Interestingly, VMAT showed a drawback in preserving the normal brain tissues for T4-stage patients. This revealed that the two treatment modalities have unique characteristics in preserving normal brain tissue, each with advantages. With better localization precision, the created CT brain template in MNI space may be beneficial for NPC patients' toxicity and dosimetric analyses., Competing Interests: None., (AJCR Copyright © 2024.)

Although TiNb 2 O 7 (TNO) with comparable operating potential and ideal theoretical capacity is considered to be the most ideal replacement for negative Li 4 Ti 5 O 12 (LTO), the low ionic and electronic conductivity still limit its practical application as satisfactory anode for lithium-ion batteries (LIBs) with high-power density. Herein, TNO nanoparticles modified by Cerium (Ce) with outstanding electrochemical performance are synthesized. The successful introduction of Ce 3+ in the lattice leads to increased interplanar spacing, refined grain size, more oxygen vacancy, and a smaller lithium diffusion barrier, which are conducive to improve conductivity of both Li + and electrons. As a result, the modified TNO reaches high reversible capacity of 256.0 mA h g -1 at 100 mA g -1 after 100 cycles, and 183.0 mA h g -1 even under 3200 mA g -1 . In particular, when the temperature drops to -20 °C, the cell undergoing 1500 cycles at a high current density of 500 mA g -1 can still reach 89.7 mA h g -1 , corresponding to a capacity decay rate per cycle of only 0.033%. This work provides a new way to improve the electrochemical properties of alternative anodes for LIBs at extreme temperature., (© 2024 Wiley‐VCH GmbH.)

This research aimed to investigate effects of different yeast culture (YC) levels on in vitro fermentation characteristics and bacterial and fungal community under high concentrate diet. A total of 5 groups were included in the experiment: control group without YC (CON), YC1 (0.5% YC proportion of substrate dry matter), YC2 (1%), YC3 (1.5%) and YC4 (2%). After 48 h of fermentation, the incubation fluids and residues were collected to analyze the ruminal fermentation parameters and bacterial and fungal community. Results showed that the ruminal fluid pH of YC2 and YC4 groups was higher (P < 0.05) than that of CON group. Compared with CON group, the microbial protein, propionate and butyrate concentrations and cumulative gas production at 48 h of YC2 group were significantly increased (P < 0.05), whereas an opposite trend of ammonia nitrogen and lactate was observed between two groups. Microbial analysis showed that the Chao1 and Shannon indexes of YC2 group were higher (P < 0.05) than those of CON group. Additionally, YC supplementation significantly decreased (P < 0.05) Succinivibrionaceae&#95;UCG-001, Streptococcus bovis and Neosetophoma relative abundances. An opposite tendency of Aspergillus abundance was found between CON and YC treatments. Compared with CON group, the relative abundances of Prevotella, Succiniclasticum, Butyrivibrio and Megasphaera elsdenii were significantly increased (P < 0.05) in YC2 group, while Apiotrichum and unclassified Clostridiales relative abundances were decreased (P < 0.05). In conclusion, high concentrate substrate supplemented with appropriate YC (1%) can improve ruminal fermentation and regulate bacterial and fungal composition., (© 2024. The Author(s).)

In recent years, extensive research efforts have been dedicated to the investigation of CdSe/CdS-based quantum-confined nanostructures, driven by their distinctive properties. The morphologies of these nanostructures have been shown to directly affect their properties, an area which has proven to be an important field of study. Herein, we report a new morphology of CdSe/CdS core-shell heterostructures in the form of a 'nanonail' - a modified nanorod-like morphology, in which a distinctive triangular head can be observed at one end of the structure. In-depth studies of this morphology reveal a material with tuneable rod length and width, as well as exceptional photoluminescent properties. Following this, we have demonstrated the ability to induce chiroptical activity via ligand exchange, revealing the important role of the specific morphology, shell thickness and chiral ligand concentration in the effect of ligand induced chirality. In addition, the cellular uptake and cytotoxicity of obtained chiral nanostructures were evaluated on human lung-derived A549 cancer cells, revealing a significant enantioselectivity in biological activity. Finally, analysis on monolayers of the material demonstrate the complete absence of FRET processes. Overall, this CdSe/CdS heterostructure is another tuneable morphology of a very important nanomaterial, one which shows great advantages and a range of potential applications.

Rapid and accurate detection of the zoonotic nematode Anisakis is poised to control its epidemic. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-associated assay shows great potential in the detection of pathogenic microorganisms. The one-tube method integrated the CRISPR system with the recombinase polymerase amplification (RPA) system to avoid the risk of aerosol pollution; however, it suffers from low sensitivity due to the incompatibility of the two systems and additional manual operations. Therefore, in the present study, the agarose hydrogel boosted one-tube RPA-CRISPR/Cas12a assay was constructed by adding the CRISPR system to the agarose hydrogel, which avoided the initially low amplification efficiency of RPA caused by the cleavage of Cas12a and achieved reaction continuity. The sensitivity was 10-fold higher than that of the one-tube RPA-CRISPR/Cas12a system. This method was used for Anisakis detection within 80 min from the sample to result, achieving point-of-care testing (POCT) through a smartphone and a portable device. This study provided a novel toolbox for POCT with significant application value in preventing Anisakis infection.

Information regarding protein expression and phosphorylation modifications in the bovine milk fat globule membrane is scarce, particularly throughout various lactation periods. This study employed a complete proteome and phosphoproteome between bovine colostrum and mature milk. A total of 11 proteins were seen in both protein expression and phosphorylation levels. There were 400 proteins identified in only protein expression, and 104 phosphoproteins identified in only phosphorylation levels. A total of 232 significant protein characteristics were identified within the proteome and significant phosphorylation sites within 86 phosphoproteins of the phosphoproteome. Biological activities and pathways primarily exhibited associations with the immune system. Simultaneously, a comprehensive analysis of proteins and phosphorylation sites using a multi-omics approach. Hence, the data we have obtained has the potential to expand our understanding of how the bovine milk fat globule membrane might be utilized as a beneficial component in dairy products., 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.)

Although conductive hydrogel-based flexible electronic devices have superb flexibility and high conductivities, they tend to malfunction in dry or frigid areas. Herein, an ultralow-temperature tolerant, antidrying, and conductive composite hydrogel is designed for electronic skin applications on the basis of the synergy of double-cross-linked polymer networks, Hofmeister effect, and electrostatic interaction and fabricated by in situ free radical polymerization of 2-acrylamido-2-methyl-1-propanesulfonic acid and acrylic acid in the presence of poly(vinyl alcohol) and conductive MXene sheets, followed by impregnation with LiCl. Thanks to the synergy of LiCl and the charged polar terminal groups of the synthesized polymers, the composite hydrogel can not only bear an ultralow temperature of -80 °C without freezing but also maintain its original mass. Meanwhile, the resultant hydrogel possesses satisfactory self-regeneration ability benefiting from the moisturizing effect of LiCl. The conductive network of MXene sheets greatly improves the ionic conductivity of the hydrogel at low temperatures, exhibiting an ionic conductivity of 1.4 S m -1 at -80 °C. Furthermore, the electronic skin assembled by the multifunctional hydrogel is efficient in monitoring human motions at -80 °C. The antifreezing and antidrying features along with favorable ionic conductivity, high tensile strength, and outstanding flexibility make the composite hydrogel promising for applications in frigid and dry regions.

Recently, studies have reported a correlation that individuals with diabetes show an increased risk of developing Alzheimer's disease (AD). Mulberry leaves, serving as both a traditional medicinal herb and a food source, exhibit significant hypoglycemic and antioxidative properties. The flavonoid compounds in mulberry leaf offer therapeutic effects for relieving diabetic symptoms and providing neuroprotection. However, the mechanisms of this effect have not been fully elucidated. This investigation aimed to investigate the combined effects of specific mulberry leaf flavonoids (kaempferol, quercetin, rhamnocitrin, tetramethoxyluteolin, and norartocarpetin) on both type 2 diabetes mellitus (T2DM) and AD. Additionally, the role of the gut microbiota in these two diseases' treatment was studied. Using network pharmacology, we investigated the potential mechanisms of flavonoids in mulberry leaves, combined with gut microbiota, in combating AD and T2DM. In addition, we identified protein tyrosine phosphatase 1B (PTP1B) as a key target for kaempferol in these two diseases. Molecular docking and molecular dynamics simulations showed that kaempferol has the potential to inhibit PTP1B for indirect treatment of AD, which was proven by measuring the IC 50 of kaempferol (279.23 μM). The cell experiment also confirmed the dose-dependent effect of kaempferol on the phosphorylation of total cellular protein in HepG2 cells. This research supports the concept of food-medicine homology and broadens the range of medical treatments for diabetes and AD, highlighting the prospect of integrating traditional herbal remedies with modern medical research.

Cancer-associated fibroblasts (CAFs) provide suitable conditions for growth of tumor cell and facilitate tumor progression. Hence, we aimed to identify a CAFs-related gene signature associated with the prognosis of patients with breast cancer (BRCA). We downloaded datasets from Gene Expression Omnibus (GEO) and confirmed the correlation between CAFs infiltration scores and prognosis. By performing weighted gene co-expression network analysis (WGCNA) and Lasso Cox regression analysis, we constructed a four-gene (COL5A3, FN1, POSTN, and RARRES2) prognostic CAFs signature model. Based on the median risk score of CAFs, patients with BRCA were divided into high- and low-risk groups. Compared with low-risk group, patients in high-risk group exhibited a poor prognosis and limited response to immunotherapy. Furthermore, patients with high CAFs risk scores were found to have a detrimental prognosis due to the induction of immunosuppressive cell infiltration, resulting in an immunosuppressive tumor microenvironment. Importantly, we found that CAFs overexpressing FN1 and POSTN significantly promoted the wound healing and invasion ability of tumor cells in vitro validation. Taking together, we identified a four-gene prognostic CAFs signature, which was proven to be a reliable indicator for prognosis and therapeutic efficacy in patients with BRCA. This study provided evidence for novel CAFs-based stromal therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Given the scarcity of novel antibiotics, the eradication of bacterial biofilm infections poses formidable challenges. Upon bacterial infection, the host restricts Fe ions, which are crucial for bacterial growth and maintenance. Having coevolved with the host, bacteria developed adaptive pathways like the hemin-uptake system to avoid iron deficiency. Inspired by this, we propose a novel strategy, termed iron nutritional immunity therapy (INIT), utilizing Ga-CT@P nanocomposites constructed with gallium, copper-doped tetrakis (4-carboxyphenyl) porphyrin (TCPP) metal-organic framework, and polyamine-amine polymer dots, to target bacterial iron intakes and starve them. Owing to the similarity between iron/hemin and gallium/TCPP, gallium-incorporated porphyrin potentially deceives bacteria into uptaking gallium ions and concurrently extracts iron ions from the surrounding bacteria milieu through the porphyrin ring. This strategy orchestrates a "give and take" approach for Ga 3+ /Fe 3+ exchange. Simultaneously, polymer dots can impede bacterial iron metabolism and serve as real-time fluorescent iron-sensing probes to continuously monitor dynamic iron restriction status. INIT based on Ga-CT@P nanocomposites induced long-term iron starvation, which affected iron-sulfur cluster biogenesis and carbohydrate metabolism, ultimately facilitating biofilm eradication and tissue regeneration. Therefore, this study presents an innovative antibacterial strategy from a nutritional perspective that sheds light on refractory bacterial infection treatment and its future clinical application., (© 2024 Wiley‐VCH GmbH.)

Background: Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC., Methods: This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS., Results: The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%)., Conclusion: Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Nitrogen-containing disinfection by-products (N-DBPs) produced in the process of drinking water disinfection are widely concerning due to the high cytotoxicity and genotoxicity. It is due to the difficulty of natural degradation of N-DBPs in water and the fact that conventional treatment systems do not effectively treat N-DBPs in drinking water. In this study, N-nitrosopyrrolidine (NPYR) in water was electrocatalytically degraded by a three-dimensional electrode reactor (3DER). This system applied graphite plates as anode and cathode. The granular activated carbon (GAC) was used as third electrode. The degradation of NPYR using a continuous flow three-dimensional electrode reactor was investigated by examining the effects of flow rate, current density, electrolyte concentration, and pollutant concentration on the degradation efficiency, energy consumption, and reaction kinetics of GAC particle electrodes. The results showed that the optimal operating conditions were flow rate = 0.45 mL/min, current density = 6 mA/cm 2 , Na 2 SO 4 concentration = 0.28 mol/L, and NPYR concentration = 20 mg/L. Under optimal conditions, the degradation of NPYR exceeded 58.84%. The main contributor of indirect oxidation was deduced from free radical quenching experiments. NPYR concentration was measured by GC-MS with DB-5 capillary column, operating in full scan monitoring mode for appropriate quantification of NPYR and intermediates. Based on the identification of reaction intermediates, a possible pathway for the electrochemical oxidation of NPYR on GAC particle electrodes was proposed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Bone metastasis (BM) is considered a poor prognostic factor of renal cell carcinoma (RCC). Confusion exists regarding how to deal with RCC patients with bone-only metastasis., Patients and Methods: The clinical data of consecutive RCC patients with bone-only metastasis at Peking University Cancer Hospital between 2006 and 2018 were retrospectively collected and analyzed., Results: Fifty-four eligible patients were screened from an RCC database of 1,878 metastatic patients. After a median follow-up of 43.6 m, 61.1% of the patients were presented with progression of prior BM or new BM. The progression-free survival (PFS) and overall survival (OS) was 16.2 m (95%CI: 11.4-21.0) and 65.2 m, respectively. For the 30 patients with oligo-metastasis (≤3 loci) and 24 ones with multiple-metastasis (>3 loci), the median OS was not reached and 42.0m (95%CI: 12.7-71.2) with statistical difference (P < 0.001). In the oligo-metastasis group, the median PFS of the 15 patients treated with local therapy and of the 13 patients treated with systemic therapy was 14.2 m (95%CI: 5.3-23.3) and 18.0 m (95%CI:15.4-20.6), respectively. In the multiple-metastasis group, the median PFS and OS of the 18 patients treated with systemic therapy was 16.6 m (95%CI: 7.5-25.7) and 63.9 m (95%CI: 21.8-106.0), respectively. Univariate analysis and multivariate analysis showed that the number of metastatic sites (oligo/multiple) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score, RCC pathological subtype were significantly associated with prognosis (P < 0.05)., Conclusion: RCC patients with bone-only metastases have a favorable prognosis. The number of metastatic sites, IMDC, RCC pathological subtype could serve as survival predictors, which might provide clue of treatment modality., Competing Interests: Declaration of competing interest Dr. Jun Guo is the member of the advisory board/consultant of MSD, Roche, Pfizer, Bayer, Novartis, Simcere, Shanghai Junshi Bioscience, Oriengene. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sarcopenic obesity (SO) is an age-related disease characterized by the coexistence of excessive adiposity and low muscle mass or function. Although obesity and sarcopenia are heritable conditions, the genetic determinants of SO have not been fully understood. We conducted a large-scale exome-wide association analysis of SO in a sequenced sample of 2 887 cases and 113 284 controls and an imputed sample of 4 003 cases and 161 990 controls in the UK Biobank cohort. Single-variant association analysis identified one locus 1q41 (lead SNP rs1417066, LYPLAL1-AS1, odds ratio [OR] = 1.15, 95% confidence interval [CI] = [1.11-1.19], p = 1.75 × 10-14) that was significantly associated with SO at the exome-wide significance level (p < 1 × 10-8). Colocalization analysis in the Genotype-Tissue Expression expression quantitative trait locus database showed that LYPLAL1-AS1 was colocalized with SO in multiple musculoskeletal-related tissues. Gene-based burden test of rare loss-of-function variants identified 5 genes at the gene-wise significance level (p < 4.3 × 10-6): PDE3B (OR = 2.48, p = 1.10 × 10-6), MYOZ3 (OR = 25.49, p = 1.41 × 10-7), SLC15A3 (OR = 4.75, p = 6.82 × 10-7), RNF130 (OR = 25.83, p = 4.07 × 10-6), and TNK2 (OR = 4.25, p = 8.75 × 10-8). Overall, our study uncovered the genetic effects of both common and rare variants on SO susceptibility, expanded existing knowledge of the genetic architecture of SO, and improved understanding of the genetic mechanisms underlying SO., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Sarcopenia is a harmful condition common among older adults for which no treatment is available. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (FN14) are known to play important roles in the pathogenesis of sarcopenia. This study investigated alterations in methylation in TWEAK and Fn14 to identify potential targets for the managing sarcopenia., Materials and Methods: Through an epidemiological investigation, we detected methylation of CpG islands (CpGs) in TWEAK and Fn14 in community-dwelling older adult of Xinjiang by bisulfite sequencing. Significant CpGs associated with sarcopenia were selected for detection in 152 older individuals by pyrosequencing. Associations between CpG methylation, plasma inflammatory marker levels, and sarcopenia were analyzed., Results: Of 38 CpGs in TWEAK and 30 CpGs in Fn14 detected in 60 individuals, 6 CpGs showed lower methylation in sarcopenia patients compared with control individuals. In 152 older adults, covariance analysis with adjustment for age, gender, triglyceride level, obesity, diabetes, and hypertension showed that the methylation levels of 6 CpGs (CpG8, CpG12, CpG13, CpG20 and CpG21of TWEAK, and CpG24 of Fn14) were significantly lower in sarcopenia patients than in control individuals. With adjustment for additional confounding factors, covariate variance analysis showed that plasma TWEAK, TNF-α and IL-10 levels in the sarcopenia group were significant higher than those in the control group (P = 0.007, P < 0.001, P = 0.003). Multivariate logistic regression analysis showed that CpG8, CpG13, CpG21, and total methylation of TWEAK (OR = 0.767, 95 % CI = 0.622-0.947; OR = 0.740, 95 % CI = 0.583-0.941; OR = 0.734, 95 % CI = 0.561-0.958; OR = 0.883, 95 % CI = 0.795-0.980) as well as CpG22 and total methylation of Fn14 were significantly associated with sarcopenia (OR = 826, 95 % CI = 0.704-0.968; OR = 0.918, 95 % CI = 0.852-0.989). From partial correlation analysis, plasma TWEAK was correlated with plasma TNF-α (r = 0.172, P = 0.042)., Conclusion: Sarcopenia is associated with hypomethylation of TWEAK and increased plasma levels of TWEAK and its downstream inflammatory factor TNF-α in a community-dwelling population of older adults in Xinjiang., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The efficacy of thrombolysis (IVT) in minor stroke (National Institutes of Health Stroke Scale score, 0-5) remains inconclusive. The aim of this study is to compare the effectiveness and safety of IVT with best medical therapy (BMT) by means of a systematic review and meta-analysis of randomized controlled trials and observational studies., Methods: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to IVT in minor stroke from inception until August 10, 2023. The primary outcome was an excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 at 90 days. The associations were calculated for the overall and preformulated subgroups by using the odds ratios (ORs). This study was registered with PROSPERO (CRD42023445856)., Results: A total of 20 high-quality studies, comprised of 13 397 patients with acute minor ischemic stroke, were included. There were no significant differences observed in the modified Rankin Scale scores of 0 to 1 (OR, 1.10 [95% CI, 0.89-1.37]) and 0 to 2 (OR, 1.16 [95% CI, 0.95-1.43]), mortality rates (OR, 0.67 [95% CI, 0.39-1.15]), recurrent stroke (OR, 0.89 [95% CI, 0.57-1.38]), and recurrent ischemic stroke (OR, 1.09 [95% CI, 0.68-1.73]) between the IVT and BMT group. There were differences between the IVT group and the BMT group in terms of early neurological deterioration (OR, 1.81 [95% CI, 1.17-2.80]), symptomatic intracranial hemorrhage (OR, 7.48 [95% CI, 3.55-15.76]), and hemorrhagic transformation (OR, 4.73 [95% CI, 2.40-9.34]). Comparison of modified Rankin Scale score of 0 to 1 remained unchanged in subgroup patients with nondisabling deficits or compared with those using antiplatelets., Conclusions: These findings indicate that IVT does not yield significant improvement in the functional prognosis of patients with acute minor ischemic stroke. Additionally, it is associated with an increased risk of symptomatic intracranial hemorrhage when compared with the BMT. Moreover, IVT may not have superiority over BMT in patients with nondisabling deficits or those using antiplatelets., Competing Interests: Disclosures Dr Nguyen reports payment or honoraria from Medtronic. Dr Nguyen serves as the president of the SVIN, associate editor of Stroke, advisory board member of Idorsia and Brainomix, co-PI of the SUMMIT MAX trial, the data and safety monitoring board member of CREST2, SELECT2, TESLA, TATUM, WE-TRUST, and ENDOLOW trials. She is also the coauthor of ARAMIS trial. Disclosures provided by Dr Nguyen in compliance with American Heart Association’s annual Journal Editor Disclosure Questionnaire are available at https://www.ahajournals.org/editor-coi-disclosures. The other authors report no conflicts.

Hepatocellular carcinoma (HCC) is a digestive tract cancer with high mortality and poor prognosis, especially in China. Current chemotherapeutic drugs lead to poor prognosis, low efficacy, and high side effects due to weak targeting specificity and rapidly formed multidrug resistance (MDR). Based on the previous studies on the doxorubicin (DOX) formulation for cancer targeting therapy, we developed a novel DOX delivery formulation for the targeting chemotherapy of HCC and DOX resistant HCC. HCSP4 was previously screened and casein kinase 2α (CK2α) was predicted as its specific target on HCC cells in our lab. In the study, miR125a-5p was firstly predicted as an MDR inhibiting miRNA, and then CK2α was validated as the target of HCSP4 and miR125a-5p using CK2α-/-HepG2 cells. Based on the above, an HCC targeting and MDR inhibiting DOX delivery liposomal formulation, HCSP4/Lipo-DOX/miR125a-5p was synthesized and tested for its HCC therapeutic efficacy in vitro. The results showed that the liposomal DOX delivery formulation targeted to HCC cells specifically and sensitively, and presented the satisfied therapeutic efficacy for HCC, particularly for DOX resistant HCC. The potential therapeutic mechanism of the DOX delivery formulation was explored, and the formulation inhibited the expression of MDR-relevant genes including ATP-binding cassette subfamily B member 1 (ABCB1, also known as P-glycoprotein), ATP-binding cassette subfamily C member 5 (ABCC5), enhancer of zeste homolog 2 (EZH2), and ATPase Na + /K + transporting subunit beta 1 (ATP1B1). Our study presents a novel targeting chemotherapeutic drug formulation for the therapy of HCC, especially for drug resistant HCC, although it is primarily and needs further study in vivo, but provided a new strategy for the development of novel anticancer drugs., (© 2024 Wiley‐VCH GmbH.)

Hepatocellular carcinoma (HCC) is the third most lethal cancer in the world. Recent studies have shown that suppression of autophagy plays an important role in the development of HCC. Ginsenoside Rk1 is a protopanaxadiol saponin isolated from ginseng and has a significant anti-tumor effect, but its role and mechanism in HCC are still unclear. In this study, a mouse liver cancer model induced by diethylnitrosamine and carbon tetrachloride (DEN + CCl 4 ) was employed to investigate the inhibitory effect of Rk1 on HCC. The results demonstrate that ginsenoside Rk1 effectively inhibits liver injury, liver fibrosis, and cirrhosis during HCC progression. Transcriptome data analysis of mouse liver tissue reveals that ginsenoside Rk1 significantly regulates the AMPK/mTOR signaling pathway, autophagy pathway, and apoptosis pathway. Subsequent studies show that ginsenoside Rk1 induces AMPK protein activation, upregulates the expression of autophagy marker LC3-II protein to promote autophagy, and then downregulates the expression of Bcl2 protein to trigger a caspase cascade reaction, activating AMPK/mTOR-induced toxic autophagy to promote cells death. Importantly, co-treatment of ginsenoside Rk1 with autophagy inhibitors can inhibit apoptosis of HCC cells, once again demonstrating the ability of ginsenoside Rk1 to promote autophagy-dependent apoptosis. In conclusion, our study demonstrates that ginsenoside Rk1 inhibits the development of primary HCC by activating toxic autophagy to promote apoptosis through the AMPK/mTOR pathway. These findings confirm that ginsenoside Rk1 is a promising new strategy for the treatment of HCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Melatonin is involved in exerting protective effects in aged-related and neurodegenerative diseases through a silent information regulator type 1 (SIRT1)-dependent pathway. However, little was known about the impact of melatonin on retinal ganglion cell (RGC) senescence and apoptosis following optic nerve crush (ONC). Thus, this study aimed to examine the effects of melatonin on RGC senescence and apoptosis after ONC and investigate the involvement of SIRT1 in this process. To study this, an ONC model was established. EX-527, an inhibitor of SIRT1, was injected intraperitoneally into mice. And melatonin was administrated abdominally into mice after ONC every day. Hematoxylin & eosin staining, retina flat-mounts and optical coherence tomography were used to evaluate the loss of retina cells/neurons. Pattern electroretinogram (p-ERG) was performed to evaluate the function of RGCs. Immunofluorescence and western blot were used to evaluate protein expression. SA-β-gal staining was employed to detect senescent cells. The results demonstrated that melatonin partially rescued the expression of SIRT1 in RGC 3 days after ONC. Additionally, melatonin administration partly rescued the decreased RGC number and ganglion cell complex thickness observed 14 days after ONC. Melatonin also suppressed ONC-induced senescence and apoptosis index. Furthermore, p-ERG showed that melatonin improved the amplitude of P50, N95 and N95/P50 following ONC. Importantly, the protective effects of melatonin were reversed when EX-527 was administered. In summary, this study revealed that melatonin attenuated RGC senescence and apoptosis through a SIRT1-dependent pathway after ONC. These findings provide valuable insights for the treatment of RGC senescence and apoptosis., 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.)

Background: The effect of a healthy lifestyle on dementia associated with multimorbidity is not well understood. Our objective is to examine whether the adoption of a healthy lifestyle could potentially reduce the elevated risk of dementia in individuals with and without multimorbidity., Methods: We utilized data from the UK Biobank cohort. A comprehensive healthy lifestyle score, ranging from 0 to 6, was generated. Cox proportional hazards models were used to examine the associations between multimorbidity, the healthy lifestyle score, and the incidence risk of dementia., Results: Over a median follow-up period of 12.5 years, 5 852 all-cause dementia were recorded. Multimorbidity including cardiovascular, metabolic, neuropsychiatric, and inflammation-related diseases was associated with a higher risk of subsequent dementia. Each additional chronic disease was associated with a hazard ratio (HR) of 1.38 (95% CI: 1.33, 1.44). Compared to individuals without multimorbidity and a healthy lifestyle score of 5-6, patients with multimorbidity and a lifestyle score of 0-1 had a significantly higher risk of dementia (HR: 3.13; 95% CI: 2.64, 3.72), but the risk was markedly attenuated among those with multimorbidity and a lifestyle score of 5-6. Among patients with 3 or more diseases, the HR for dementia was 0.53 (95%CI: 0.42, 0.68) when comparing a lifestyle score of 5-6 to 0-1. And we observed more pronounced association between them among people younger than 60 years old., Conclusions: Adherence to a combination of healthy lifestyle factors, especially at a young age, was associated with a significantly lower risk of dementia among participants with multimorbidity., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study aims to establish a screening method for canine distemper virus (CDV) microneutralizing activity suitable for microvolume samples., Methods: This method is based on the Indirect immunofluorescence assay (IFA) established on Vero-slam cells. First, by comparing the sensitivities of CDV neutralizing monoclonal antibody (1C42H11) and NP protein monoclonal antibody (CDV-NP) in IFA experiments, CDV-NP was selected as the primary antibody. Then, by detecting the infection rates of multi-concentrations of CDV neutralized with water, the minimum CDV concentration with an infection rate greater than 90% was defined as the minimum stable infection concentration, which was used as the neutralizing solution for this method. Finally, the CDV-positive neutralizing serum (neutralizing titer 1:708) was diluted into multiple dilution groups as test samples, and then neutralized in equal volumes with the neutralizing solution to detect the neutralizing activity detection rates of each dilution group and the lowest detection limit of this method., Results: The results showed that the neutralizing activity of serum with a CDV neutralizing titer of 1:708 diluted 2 12 times was the lowest limit of detection, and the detection rate of microneutralizing activity was 63.54 ± 4.774%., Conclusion: This study established an economical, stable, and easy-to-operate CDV microneutralizing activity high-throughput screening method, laying a methodological foundation for the development of native CDV neutralizing antibodies based on single B cells., 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.)

Background: A pineal region tumor is a rare intracranial tumor, and its specific location leads to its own characteristics. This study aimed to provide some insight for medical practice in the care of pineal region tumors. We investigated the key epidemiological characteristics and survival prognosis of pineal tumors based on the epidemiological data from the Surveillance, Epidemiology, and End Results database., Methods: Data of pineal region tumor patients from 1975 to 2019 were extracted from the Surveillance, Epidemiology, and End Results database. The data were divided into 3 pathologic groups: germ cell tumors, pineal parenchymal tumors, and other. The patients' overall survival (OS) was analyzed using the Kaplan-Meier method. The prognostic effects of the patient characteristics on OS were explored using the Cox proportional hazard model. The analysis results are presented as tabular data, Kaplan-Meier plots, forest plots, and nomograms. A calibration curve was used to verify the nomograms. All analyses were performed for all patients overall and stratified by pathological group using SPSS and R language., Results: Based on the predefined inclusion and exclusion criteria, 628 patients were included in this study, of whom 440 (70.1%) were male and 188 (29.9%) were female. Most patients were aged 0-19 years. The pathological type was germinoma for 225 patients (35.8%). Age, surgery, behavioral code, and pathology were significant factors for OS. A calibration curve was used to verify that the nomograms had a good prediction effect., Conclusions: An intuitive nomogram was developed and verified and can predict the prognosis of patients with pineal tumors., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aspirin has shown potential for cancer prevention, but a recent large randomized controlled trial found no evidence for a reduction in cancer risk. Given the anti-inflammatory effects of aspirin, systemic inflammatory diseases (SIDs), such as osteoporosis, cardiovascular diseases, and metabolic diseases, could potentially modify the aspirin-cancer link. To investigate the impact of aspirin in people with SIDs, we conducted an observational study on a prospective cohort of 478,615 UK Biobank participants. Individuals with at least one of the 41 SIDs displayed a higher cancer risk than those without SIDs. Regular aspirin use showed protective effects exclusively in patients with SID, contrasting an elevated risk among their non-SID counterparts. Nonetheless, aspirin use demonstrated preventative potential only for 9 of 21 SID-associated cancer subtypes. Cholesterol emerged as another key mediator linking SIDs to cancer risk. Notably, regular statin use displayed protective properties in patients with SID but not in their non-SID counterparts. Concurrent use of aspirin and statins exhibited a stronger protective association in patients with SID, covering 14 common cancer subtypes. In summary, patients with SIDs may represent a population particularly responsive to regular aspirin and statin use. Promoting either combined or individual use of these medications within the context of SIDs could offer a promising chemoprevention strategy.