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DNA damage repair plays a key role in maintaining genomic stability and integrity. Flap endonuclease 1 (FEN1) is a core protein in the base excision repair (BER) pathway and participates in Okazaki fragment maturation during DNA replication. Several studies have implicated FEN1 in the regulation of other DNA repair pathways, including homologous recombination repair (HRR) and non-homologous end joining (NHEJ). Abnormal expression or mutation of FEN1 in cells can cause a series of pathological responses, leading to various diseases, including cancers. Moreover, overexpression of FEN1 contributes to drug resistance in several types of cancers. All this supports the hypothesis that FEN1 could be a therapeutic target for cancer treatment. Targeting FEN1 has been verified as an effective strategy in mono or combined treatment of cancer. Small-molecule compounds targeting FEN1 have also been developed and detected in cancer regression. In this review, we summarize the recent development of small-molecule inhibitors targeting FEN1 in recent years, thereby expanding their therapeutic potential and application.

We explored the associations between the risk of lower urinary tract symptoms suggestive of benign prostatic hyperplasia(LUTS/BPH) and the number and class of chronic diseases via cross-sectional and longitudinal studies.This study included 5197 men aged ≥ 45 years from the China Health and Retirement Longitudinal Study(CHARLS) 2011 with a 7-year follow-up. We multidimensionally investigated the relationships between LUTS/BPH and multimorbidity via latent class analysis, generalized additive analysis and causal mediation analysis. Latent class analysis identified four morbidity classes as follows: minimal or least common diseases (class 1, N  = 4160, reference), dominant chronic lung diseases(class 2, N  = 152), multiple chronic diseases(class 3, N  = 387), and dominant heart diseases or risks(class 4, N  = 498). In both the cross-sectional and cohort studies, the risk of LUTS/BPH increased in a dose-dependent manner with the number of chronic diseases. All multivariable-adjusted analyses suggested that three other classes had significantly greater risks of LUTS/BPH than did class 1. In the cross-sectional study, the risk of LUTS/BPH increased by 3.19 times(95%CI: 2.41 to 4.21) in class 3 than in class 1. Causal mediation analyses revealed that depression significantly mediated the association between LUTS/BPH and multimorbidity. Our results suggest that both the number and class of chronic diseases significantly affect the risk of LUTS/BPH.

Apurinic/apyrimidinic endonuclease 1 (APE1) plays a critical role in the base excision repair (BER) pathway, which is responsible for the excision of apurinic sites (AP sites). In non-small cell lung cancer (NSCLC), APE1 is highly expressed and associated with poor patient prognosis. The suppression of APE1 could lead to the accumulation of unrepaired DNA damage in cells. Therefore, APE1 is viewed as an important marker of malignant tumors and could serve as a potent target for the development of antitumor drugs. In this study, we performed a high-throughput virtual screening of a small-molecule library using the three-dimensional structure of APE1 protein. Using the AP site cleavage assay and a cell survival assay, we identified a small molecular compound, NO.0449-0145, to act as an APE1 inhibitor. Treatment with NO.0449-0145 induced DNA damage, apoptosis, pyroptosis, and necroptosis in the NSCLC cell lines A549 and NCI-H460. This inhibitor was also able to impede cancer progression in an NCI-H460 mouse model. Moreover, NO.0449-0145 overcame both cisplatin- and erlotinib-resistance in NSCLC cell lines. These findings underscore the importance of APE1 as a therapeutic target in NSCLC and offer a paradigm for the development of small-molecule drugs that target key DNA repair proteins for the treatment of NSCLC and other cancers.

The extracellular matrix (ECM) is a significant factor in cancer progression. Collagens, as the main component of the ECM, are greatly remodeled alongside cancer development. More and more studies have confirmed that collagens changed from a barrier to providing assistance in cancer development. In this course, collagens cause remodeling alongside cancer progression, which in turn, promotes cancer development. The interaction between collagens and tumor cells is complex with biochemical and mechanical signals intervention through activating diverse signal pathways. As the mechanism gradually clears, it becomes a new target to find opportunities to diagnose and treat cancer. In this review, we investigated the process of collagen remodeling in cancer progression and discussed the interaction between collagens and cancer cells. Several typical effects associated with collagens were highlighted in the review, such as fibrillation in precancerous lesions, enhancing ECM stiffness, promoting angiogenesis, and guiding invasion. Then, the values of cancer diagnosis and prognosis were focused on. It is worth noting that several generated fragments in serum were reported to be able to be biomarkers for cancer diagnosis and prognosis, which is beneficial for clinic detection. At a glance, a variety of reported biomarkers were summarized. Many collagen-associated targets and drugs have been reported for cancer treatment in recent years. The new targets and related drugs were discussed in the review. The mass data were collected and classified by mechanism. Overall, the interaction of collagens and tumor cells is complicated, in which the mechanisms are not completely clear. A lot of collagen-associated biomarkers are excavated for cancer diagnosis. However, new therapeutic targets and related drugs are almost in clinical trials, with merely a few in clinical applications. So, more efforts are needed in collagens-associated studies and drug development for cancer research and treatment.

Background Depression is associated with an increased risk of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). Whether the dynamic nature of depression affects the incidence of LUTS/BPH remains unknown. A four-year cohort study based on the China Health and Retirement Longitudinal Study (CHARLS) was conducted to assess their association. Methods This study included 3433 Chinese men from the CHARLS 2011, representative of > 95 million individuals. All eligible individuals underwent three assessments of LUTS/BPH and depression in 2011, 2013 and 2015. The dynamic nature of depression was classified as acute depression with remission, acute depression with recurrence, or chronic major depression. Weighted, generalized additive analyses with three binomial models were used to investigate the relationship between LUTS/BPH and the dynamic nature of depression. Results During the four-year follow-up, 11.5% (95% confidence interval [95% CI] = 9.5-13.3%) of Chinese men were diagnosed with newly incident LUTS/BPH. Meanwhile, there were 60.6% (95% CI = 58.5-62.7%) of the individuals without depression and 8.9% (95% CI = 7.9-10%) of the individuals with chronic major depression. A total of 25.1% (95% CI = 23.4-26.9%) and 5.4% (95% CI = 4.6-6.3%) of the individuals were categorized as acute depression with remission and recurrence. After weighted, adjusted all included confounding risk factors, chronic major depression (RR = 1.63, 95% CI = 1.14–2.33, P  < 0.01) but not acute depression with remission (RR = 1.2, 95% CI = 0.92–1.56, P  = 0.18) and recurrence (RR = 1.32, 95% CI = 0.82–2.10, P  = 0.26) significantly increased the incidence of LUTS/BPH compared with no depression. The subgroup analysis showed that the above relationships appeared to be evident among Chinese men < 60 years. Conclusions Our results suggest that the dynamic nature of depression has a different effect on the incidence of LUTS/BPH. The monitoring and treatment of depression are important in preventing LUTS/BPH.

Stroke is a significant cause of disability worldwide, and stroke survivors often experience severe motor impairments. Lower limb rehabilitation exoskeleton robots provide support and balance for stroke survivors and assist them in performing rehabilitation training tasks, which can effectively improve their quality of life during the later stages of stroke recovery. Lower limb rehabilitation exoskeleton robots have become a hot topic in rehabilitation therapy research. This review introduces traditional rehabilitation assessment methods, explores the possibility of lower limb exoskeleton robots combining sensors and electrophysiological signals to assess stroke survivors' rehabilitation objectively, summarizes standard human-robot coupling models of lower limb rehabilitation exoskeleton robots in recent years, and critically introduces adaptive control models based on motion intent recognition for lower limb exoskeleton robots. This provides new design ideas for the future combination of lower limb rehabilitation exoskeleton robots with rehabilitation assessment, motion assistance, rehabilitation treatment, and adaptive control, making the rehabilitation assessment process more objective and addressing the shortage of rehabilitation therapists to some extent. Finally, the article discusses the current limitations of adaptive control of lower limb rehabilitation exoskeleton robots for stroke survivors and proposes new research directions.

User requirements serve as the primary reference content in product design. The effective capture of crucial user requirements, followed by the development of a product technical solution aligned with these requirements, stands as a pivotal approach to enhancing design efficiency. In order to explore the problem of generating and decision-making of product technical solutions in the case of complex user demands, this study constructs a user requirements driven product optimization design model, which is used to complete the generation and decision-making of product design solutions in a more reasonable way. The model unfolds across three key stages: Firstly, a user requirements importance ranking system is crafted leveraging Kano Model and Pairwise Analysis. Next, employing the Functional Analysis System Techniques (FAST) theory and the Quality Function Deployment (QFD) theory, user requirements undergo transformation into technical solutions. Finally, these technical solutions are amalgamated into diverse technical combinations, with decisions facilitated by a game theory model to yield the optimal overall design solution. The new optimal design model reduces the influence of subjectivity and ambiguity in the process of user requirements analysis, increases the reliability of the transformation of user requirements into technical solutions, and improves the efficiency of the generation and decision-making of product design solutions under multiobjective situations. The model proposed in this study is exemplified through the development of a medicated bath water heater. Results indicate that the technical solution derived from the model surpasses similar products in terms of user satisfaction, thereby validating its feasibility.

Methyltransferase-like 3 (METTL3) and N 6 -methyladenosine (m 6 A) are involved in many types of biological and pathological processes, including DNA repair. However, the function and mechanism of METTL3 in DNA repair and chemotherapeutic response remain largely unknown. In present study, we identified that METTL3 participates in the regulation of homologous recombination repair (HR), which further influences chemotherapeutic response in both MCF-7 and MDA-MB-231 breast cancer (BC) cells. Knockdown of METTL3 sensitized these BC cells to Adriamycin (ADR; also named as doxorubicin) treatment and increased accumulation of DNA damage. Mechanically, we demonstrated that inhibition of METTL3 impaired HR efficiency and increased ADR-induced DNA damage by regulating m6A modification of EGF/RAD51 axis. METTL3 promoted EGF expression through m6A modification, which further upregulated RAD51 expression, resulting in enhanced HR activity. We further demonstrated that the m6A ‘reader,’ YTHDC1, bound to the m6A modified EGF transcript and promoted EGF synthesis, which enhanced HR and cell survival during ADR treatment in BC. Our findings reveal a pivotal mechanism of METTL3-mediated HR and chemotherapeutic drug response, which may contribute to cancer therapy.

This study investigated the relationships between dietary sodium intake and the incidence and prevalence of interstitial lung disease (ILD) and pulmonary sarcoidosis using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. This study assessed the strength of the abovementioned relationships via LASSO analysis and a generalized additive model with Poisson regression and determined the nonlinear and lagged effects via a distributed lag nonlinear model (DLNM). In the past three decades, global dietary sodium intake has decreased gradually. Two LASSO and generalized additive analyses both suggested that dietary sodium intake is obviously correlated with the incidence and prevalence of ILD and pulmonary sarcoidosis. The overall exposure‒response curve revealed a dose‒effect relationship between dietary sodium intake and the incidence and prevalence of ILD and pulmonary sarcoidosis. The maximum lag-specific RR of extremely high dietary sodium intake was 1.75 (95% CI: 1.61–1.91, lag 0 year) for incidence and 3.19 (95% CI: 2.24–4.53, lag 0 year) for prevalence relative to the reference. Our study suggests that dietary sodium intake is positively associated with the incidence and prevalence of ILD and pulmonary sarcoidosis. These findings may have important policy implications for dietary sodium intake-reduction strategies to decrease the burden of respiratory diseases and promote public health.

The identification of key points in the human body is vital for sports rehabilitation, medical diagnosis, human–computer interaction, and related fields. Currently, depth cameras provide more precise depth information on these crucial points. However, human motion can lead to variations in the positions of these key points. While the Mediapipe algorithm demonstrates effective anti-shake capabilities for these points, its accuracy can be easily affected by changes in lighting conditions. To address these challenges, this study proposes an illumination-adaptive algorithm for detecting human key points through the fusion of multi-source information. By integrating key point data from the depth camera and Mediapipe, an illumination change model is established to simulate environmental lighting variations. Subsequently, the fitting function of the relationship between lighting conditions and adaptive weights is solved to achieve lighting adaptation for human key point detection. Experimental verification and similarity analysis with benchmark data yielded R2 results of 0.96 and 0.93, and cosine similarity results of 0.92 and 0.90. With a threshold range of 8, the joint accuracy rates for the two rehabilitation actions were found to be 89% and 88%. The experimental results demonstrate the stability of the proposed method in detecting key points in the human body under changing illumination conditions, its anti-shake ability for human movement, and its high detection accuracy. This method shows promise for applications in human–computer interaction, sports rehabilitation, and virtual reality.