Septic myocardial injury is a common complication of severe sepsis, which occurs in about 50% of cases. Patients with this disease may experience varying degrees of myocardial damage. Annexin-A1 short peptide (ANXA1sp), with a molecular structure of Ac-Gln-Ala-Tyr, has been reported to exert an organ protective effect in the perioperative period by modulating sirtuin-3 (SIRT3). Whether it possesses protective activity against sepsis-induced cardiomyopathy is worthy of study. This study aimed to investigate whether ANXA1sp exerts its anti-apoptotic effect in septic myocardial injury in vitro and in vivo via regulating SIRT3. In this study, we established in vivo and in vivo models of septic myocardial injury based on C57BL/6 mice and primary cardiomyocytes by lipopolysaccharide (LPS) induction. Results showed that ANXA1sp pretreatment enhanced the seven-day survival rate, improved left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), and cardiac output (CO), and reduced the levels of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH). Western blotting results revealed that ANXA1sp significantly increased the expression of SIRT3, Bcl-2, and downregulated Bax expression. TUNEL staining and flow cytometry results showed that ANXA1sp could attenuate the apoptosis rate of cardiomyocytes, whereas this anti-apoptotic effect was significantly attenuated after SIRT3 knockout. To sum up, ANXA1sp can alleviate LPS-induced myocardial injury by reducing myocardial apoptosis via SIRT3 upregulation.

Lung cancer stands as a formidable global health challenge, necessitating innovative therapeutic strategies. Polyphenols, bioactive compounds synthesized by plants, have garnered attention for their diverse health benefits, particularly in combating various cancers, including lung cancer. The advent of whole-genome and transcriptome sequencing technologies has illuminated the pivotal roles of long noncoding RNAs (lncRNAs), operating at epigenetic, transcriptional, and posttranscriptional levels, in cancer progression. This review comprehensively explores the impact of polyphenols on both oncogenic and tumor-suppressive lncRNAs in lung cancer, elucidating on their intricate regulatory mechanisms. The comprehensive examination extends to the potential synergies when combining polyphenols with conventional treatments like chemotherapy, radiation, and immunotherapy. Recognizing the heterogeneity of lung cancer subtypes, the review emphasizes the need for the integration of nanotechnology for optimized polyphenol delivery and personalized therapeutic approaches. In conclusion, we collect the latest research, offering a holistic overview of the evolving landscape of polyphenol-mediated modulation of lncRNAs in lung cancer therapy. The integration of polyphenols and lncRNAs into multidimensional treatment strategies holds promise for enhancing therapeutic efficacy and navigating the challenges associated with lung cancer treatment.

Tendon injuries are pervasive orthopedic injuries encountered by the general population. Nonetheless, recovery after severe injuries, such as Achilles tendon injury, is limited. Consequently, there is a pressing need to devise interventions, including biomaterials, that foster tendon healing. Regrettably, tissue engineering treatments have faced obstacles in crafting appropriate tissue scaffolds and efficacious nanomedical approaches. To surmount these hurdles, an innovative injectable hydrogel (CP@SiO2), comprising puerarin and chitosan through in situ self-assembly, is pioneered while concurrently delivering mesoporous silica nanoparticles for tendon healing. In this research, CP@SiO2 hydrogel is employed for the treatment of Achilles tendon injuries, conducting extensive in vivo and in vitro experiments to evaluate its efficacy. This reults demonstrates that CP@SiO2 hydrogel enhances the proliferation and differentiation of tendon-derived stem cells, and mitigates inflammation through the modulation of macrophage polarization. Furthermore, using histological and behavioral analyses, it is found that CP@SiO2 hydrogel can improve the histological and biomechanical properties of injured tendons. This findings indicate that this multifaceted injectable CP@SiO2 hydrogel constitutes a suitable bioactive material for tendon repair and presents a promising new strategy for the clinical management of tendon injuries.

Given multifunction of copper (Cu) contributing to all stages of the physiology of wound healing, Cu-based compounds have great therapeutic potentials to accelerate the wound healing, but they must be limited to a very low concentration range to avoid detrimental accumulation. Additionally, the cellular mechanism of Cu-based compounds participating the healing process remains elusive. In this study, copper oxide nanoparticles (CuONPs) were synthesized to mimic the multiple natural enzymes and trapped into PEG-b-PCL polymersomes (PS) to construct cupric-polymeric nanoreactors (CuO@PS) via a direct hydration method, thus allowing to compartmentalize Cu-based catalytic reactions in an isolated space to improve the efficiency, selectivity, recyclability as well as biocompatibility. While nanoreactors trafficked to lysosomes following endocytosis, the released Cu-based compounds in lysosomal lumen drove a cytosolic Cu+ influx to mobilize Cu metabolism mostly via Atox1-ATP7a/b-Lox axis, thereby activating the phosphorylation of mitogen-activated protein kinase 1 and 2 (MEK1/2) to initiate downstream signaling events associated with cell proliferation, migration and angiogenesis. Moreover, to facilitate to lay on wounds, cupric-polymeric nanoreactors were finely dispersed into a thermosensitive Pluronic F127 hydrogel to form a composite hydrogel sheet that promoted the healing of chronic wounds in diabetic rat models. Hence, cupric-polymeric nanoreactors represented an attractive translational strategy to harness cellular Cu metabolism for chronic wounds healing.

Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe3O4@Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab1-CEA, Ab1-AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL-1-100 ng·mL-1 with detection limits of 33.34 and 17.02 fg·mL-1 (S/N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.

Abstract Background Osteoporosis (OP) is a prevalent disease that increases the risk of fractures and affects quality of life. Although there are many factors that contribute to OP, there are fewer studies on the relationship between oxidative balance score (OBS) and OP. Methods We conducted a cross-sectional analysis to examine the association of OBS with the prevalence of OP among U.S. adults using National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2020. A final sample of 18,837 participants was included after exclusions. OBS was calculated from dietary and lifestyle data, and OP status was determined using bone mineral density (BMD) measurements. Logistic regression models and restricted cubic spline (RCS) analyses were used to explore the association between OBS and OP after adjusting for confounders. Results Our study demonstrated an inverse association between OBS and the prevalence of OP. For every unit increase in OBS, there was a 3% reduction in the odds of OP after adjustment (OR = 0.97, 95%CI: 0.96–0.99). Higher dietary OBS was associated with reduced OP risk, while an improved lifestyle OBS corresponded to higher OP incidence (P < 0.05). A linear inverse relationship between continuous OBS values and OP risk was observed, and subgroup analyses revealed that females experienced more pronounced protection as OBS increased. Conclusion The present study suggests an inverse relationship between OBS and OP in adults, with dietary OBS inversely linked to OP prevalence and lifestyle OBS positively associated. In addition, the association between OBS and OP differed between sexes.

Abstract Background: The incidence of colorectal cancer (CRC) is increasing steadily. This is corroborated by increasing evidence that establishes a connection between the regulation of immunocytes and the advancement of CRC. However, the exact underlying mechanisms remain unclear. Hence, this study aimed to elucidate the link between immune cells and vulnerability to CRC through the application of Mendelian randomization (MR) analysis. Methods Existing genome-wide association studies (GWAS) have provided summary data on immune cells and CRC in European populations. The ebi-a-GCST90018808 cohort was designated the discovery cohort, while the finn-b-C3_COLORECTAL cohort was the validation cohort. Only single nucleotide polymorphisms (SNPs) that satisfied the following conditions were selected as instrumental variables (IVs): a p-value less than 1×10–5, a linkage disequilibrium coefficient (r2) less than 0.001, and a linkage disequilibrium region width of 10000 kb. The cornerstone analytical methodology used was inverse variance weighting (IVW), which was reinforced by the MR-Egger method to assess the causality of effects. Heterogeneity analysis was performed utilizing I2 and Cochran's Q tests. To assess pleiotropy, the MR-Egger method's intercept was utilized, complemented by sensitivity evaluation through a leave-one-out approach. The two datasets were combined for meta-analysis to further validate whether the two immune cell traits were consistent between the two cohorts. Results In the discovery and validation cohorts, a causal association was found between CD25 expression on unswitched memory B cells and CD25++ CD45RA- CD4 not regulatory T cell absolute count, resulting in a decreased risk of CRC. Heterogeneity analysis indicated I2 < 50% and P >0.05 according to Cochran's Q test, suggesting no heterogeneity among the IVs. The intercept obtained from the MR‒Egger analysis showed no significant difference from zero, suggesting a negligible influence of horizontal pleiotropy on the IVs. A meta-analysis was conducted to amalgamate the aggregated data from both datasets, further corroborating the influence of the two immune cell traits in mitigating CRC risk. Conclusion The results from MR analysis reveal that CD25 expression on unswitched memory B cells and CD25++ CD45RA- CD4 not regulatory T cell absolute count are intricately associated with a reduced risk of CRC.

Background: Actinidia eriantha Benth is a widely used natural product from Traditional Chinese Medicine in the Actinidiaceae family. However, its wild resources have been declining due to over-exploitation. It has become urgent to investigate the genetic diversity for the conservation of A. eriantha, to evaluate the current species and discover strategies for preservation. Methods: The internal transcribed spacer (ITS) was used to evaluate the genetic diversity among and within populations of this species. Dnasp, PERMUT and Arlequin 3.0 software were used to calculate the genetic diversity index, and MEGA 5.0 software was used to construct the neighbor-joining (NJ) tree. Results: A total of 27 haplotypes were obtained by ITS sequence analysis of 12 populations, and the most frequently haplotype observed was H1. AMOVA analysis revealed that the genetic variation rates were 10.91% (FST = 0.22290) and 77.71% (FSC = 0.12306) among and within populations, respectively, with high genetic diversity at the species level (Hd = 0.692). The genetic distance among populations ranged from 0 to 0.004. The results of Permut analysis showed that there was no significant correlation between genetic distance and geographic distance (NST > GST). The NJ tree was divided into two Clades (Clade A and Clade B), Clade B has obvious geographical specificity, and haplotypes of this clade are all specific to the GX-ZY population. Four types were found according to ITS sequences of A. eriantha, haplotypes H1 and H5 were ancient haplotypes. Conclusion: Our findings indicated that genetic diversity within populations was higher than observed among populations. This study is significant for further research endeavors focused on the efficient collection and preservation of wild resources of A. eriantha.