Search

Abstract Diabetes is a global chronic disease that seriously endangers human health and characterized by abnormally high blood glucose levels in the body. Diabetic wounds are common complications which associate with impaired healing process. Biomarkers monitoring of diabetic wounds is of great importance in the diabetes management. However, actual monitoring of biomarkers still largely relies on the complex process and additional sophisticated analytical instruments. In this work, we prepared hydrogels composed of different modules, which were designed to monitor different physiological indicators in diabetic wounds, including glucose levels, pH, and temperature. Glucose monitoring was achieved based on the combination of photonic crystal (PC) structure and glucose-responsive hydrogels. The obtained photonic crystal hydrogels (PCHs) allowed visual monitoring of glucose levels in physiological ranges by readout of intuitive structural color changes of PCHs during glucose-induced swelling and shrinkage. Interestingly, the glucose response of double network PCHs was completed in 15 min, which was twice as fast as single network PCHs, due to the higher volume fraction of glucose-responsive motifs. Moreover, pH sensing was achieved by incorporation of acid-base indicator dyes into hydrogels; and temperature monitoring was obtained by integration of thermochromic powders in hydrogels. These hydrogel modules effectively monitored the physiological levels and dynamic changes of three physiological biomarkers, both in vitro and in vivo during diabetic wound healing process. The multifunctional hydrogels with visual monitoring of biomarkers have great potential in wound-related monitoring and treatment. Graphical abstract

Abstract The aim of this study was to identify key genes and investigate the immunological mechanisms of atopic dermatitis (AD) at the molecular level via bioinformatics analysis. Gene expression profiles (GSE32924, GSE107361, GSE121212, and GSE230200) were obtained for screening common differentially expressed genes (co-DEGs) from the gene expression omnibus database. Functional enrichment analysis, protein–protein interaction network and module construction, and identification of common hub genes were performed. Hub genes were validated using receiver operating characteristic curve analysis based on GSE130588 and GSE16161. NetworkAnalyst was used to detect microRNAs (miRNAs) and transcription factors (TFs) associated with the hub genes. The immune cell infiltration was analyzed using the CIBERSORT algorithm to further analyze the correlation between hub genes and immune cells. A total of 146 co-DEGs were obtained, showing significant enrichment in cytokine–cytokine receptor interaction and JAK-STAT signaling pathway. Seven hub genes were identified by Cytoscape and validated with external datasets. Subsequent prediction of miRNAs and TFs targeting these hub genes revealed their regulatory roles. Analysis of immune cell infiltration and correlation revealed a significant positive correlation between CCL22 expression and the number of dendritic cells activated. The identified hub genes represent potential diagnostic and therapeutic targets in the immunological pathogenesis of AD.

BACKGROUND: Exertional heat stroke (EHS) is a clinical entity characterized by abnormalities of the central nervous system (CNS) and is associated with multiple organ injury, some of which may be irreversible. It is valuable to establish an optimized model of EHS that is able to induce and assess damage to the CNS and multiple organs. METHODS: We induced EHS by using an environmental chamber with adjustable temperature and humidity and a mice forced running wheel. The endpoint for the EHS was defined as either exhaustion or a core temperature of 42.5°C being reached. Injury to the liver, kidney, and CNS of mice in the EHS group was revealed through pathological studies using hematoxylin and eosin staining of harvested organs at different time points and detection of biomarkers. The depressive-like behavior of EHS mice was assessed through open field tests, forced swimming tests, and tail suspension tests. RESULTS: The favorable environmental conditions for induction of EHS based on this presented model are 38°C, 70% RH. The EHS mice developed thermoregulatory dysfunction and experienced a significantly higher weight loss ratio compared to the SHE (sham heat exercise) group. The liver, kidney, and brain tissues of EHS mice were significantly damaged, and the pathological damage scores for each organ were significantly higher than those of the SHE group. In the open field test (OFT), compared to the SHE group, there was a significant reduction in the number and time of EHS mice entering the center of the open field. Additionally, there was a significant increase in immobile time during forced swimming test (FST) and tail suspension test (TST). CONCLUSION: This study presents an improved animal model that has the potential to assess for neurological and multiple organ injury caused by EHS and simultaneously, while accurately reflecting the clinical characteristics observed in EHS patients.

Abstract Erectile dysfunction (ED) is a prevalent type of sexual dysfunction, and continuous monitoring of penile tumescence and rigidity during spontaneous nocturnal erections is crucial for its diagnosis and classification. However, the current clinical standard device, limited by its active mechanical load, is bulky and nonwearable and strongly interferes with erections, which compromises both monitoring reliability and patient compliance. Here, we report a wearable adaptive rigidity monitoring (WARM) system that employs a measurement principle without active loads, allowing for the assessment of penile tumescence and rigidity through a specifically designed elastic dual-ring sensor. The dual-ring sensor, comprising two strain-sensing rings with distinct elastic moduli, provides high resolution (0.1%), robust mechanical and electrical stability (sustaining over 1000 cycles), and strong interference resistance. An integrated flexible printed circuit (FPC) collects and processes sensing signals, which are then transmitted to the host computer via Bluetooth for ED assessment. Additionally, we validated the WARM system against the clinical standard device using both a penile model and healthy volunteers, achieving high consistency. Furthermore, the system facilitates the continuous evaluation of penile erections during nocturnal tumescence tests with concurrent sleep monitoring, demonstrating its ability to minimize interference with nocturnal erections. In conclusion, the WARM system offers a fully integrated, wearable solution for continuous, precise, and patient-friendly measurement of penile tumescence and rigidity, potentially providing more reliable and accessible outcomes than existing technologies. Erectile dysfunction (ED) is a prevalent sexual dysfunction, and continuous monitoring of penile tumescence and rigidity during spontaneous nocturnal erections is crucial for its diagnosis and classification. However, the current clinical standard device, limited by its active mechanical load, is bulky, nonwearable, and creates pronounced interference with erections, which compromises both monitoring reliability and patient compliance. Here, we report a wearable adaptive rigidity monitoring (WARM) system (Fig. 1a) that employs a measurement principle without active loads (Fig. 1b), allowing for the assessment of penile tumescence and rigidity through a specifically designed elastic dual-ring sensor. The dual-ring sensor, comprising two strain-sensing rings with distinct elastic moduli, provides high resolution (0.1%), robust mechanical and electrical stability (sustaining over 1000 cycles), and strong interference resistance. Additionally, we validate the WARM system against the clinical standard device using both a penile model and healthy volunteers, achieving high consistency. Furthermore, the system facilitates the continuous evaluation of penile erections during nocturnal tumescence tests, with concurrent sleep monitoring, demonstrating its ability to minimize interference with nocturnal erections (Fig. 1c). In conclusion, the WARM system offers a fully integrated, wearable solution for continuous, precise, and patient-friendly measurement of penile tumescence and rigidity, potentially providing more reliable and accessible outcomes than those from existing technologies.

Objective To explore the application value of transesophageal echocardiography （TEE） for evaluating hemodialysis tunneled cuffed catheter （TCC） dysfunction. Methods From March 1, 2020 to July 31, 2022, 28 patients hospitalized at Central Municipal Hospital for hemodialysis with tunneled cuffed catheter （TCC） dysfunction. Both TEE and digital subtraction angiography（DSA） were performed for observing the status of catheter routing, thrombus, fibrin sheath and central venous disease, etc. Positive criteria for TEE/DSA if one or more of the following:（1）catheter-related thrombosis （CRT）; （2） fibrin sheath around duct; （3） central venous stenosis; （4）narrow chamber junction;（5）catheter in an inappropriate position. With DSA as a gold standard, sensitivity, specificity, accuracy, positive predictive value and negative predictive value of TEE results were analyzed. Receiver operating characteristic（ROC） curve and area under ROC curve（AUC） were employed for examining the accuracy of TEE and verifying the consistency of two inspection results. Results Among them,18 were TEE positive and 16 DSA positive. As compared with DSA results, TEE had a sensitivity of 87.5%, a specificity of 66.7%, an accuracy of 78.6%, a positive predictive value of 77.8% and a negative predictive value of 80%. AUC of 0.771 [95%CI （0.582, 0.960）], P = 0.016;Kappa = 0.553, P = 0.003] hinted at consistency between TEE/DSA results. Conclusion As an important modality of evaluating TCC dysfunction, TEE offers the advantages of non-invasiveness, affordability and convenience. It may guide the diagnosis and treatment of TCC dysfunction and is worthy of wider popularization.

Abstract Many biological problems are understudied due to experimental limitations and human biases. Although deep learning is promising in accelerating scientific discovery, its power compromises when applied to problems with scarcely labeled data and data distribution shifts. We develop a deep learning framework—Meta Model Agnostic Pseudo Label Learning (MMAPLE)—to address these challenges by effectively exploring out-of-distribution (OOD) unlabeled data when conventional transfer learning fails. The uniqueness of MMAPLE is to integrate the concept of meta-learning, transfer learning and semi-supervised learning into a unified framework. The power of MMAPLE is demonstrated in three applications in an OOD setting where chemicals or proteins in unseen data are dramatically different from those in training data: predicting drug-target interactions, hidden human metabolite-enzyme interactions, and understudied interspecies microbiome metabolite-human receptor interactions. MMAPLE achieves 11% to 242% improvement in the prediction-recall on multiple OOD benchmarks over various base models. Using MMAPLE, we reveal novel interspecies metabolite-protein interactions that are validated by activity assays and fill in missing links in microbiome-human interactions. MMAPLE is a general framework to explore previously unrecognized biological domains beyond the reach of present experimental and computational techniques.

Abstract. Background:. Female breast and five gynecological cancers remain substantial burden in China and worldwide. GLOBOCAN 2022 has recently updated the estimates of cancer burden. This study aims to depict the profiles of disease burden and to compare the age-specific rates of female breast and five gynecological cancers in China with those in other countries. Methods:. The latest estimates of incidence and mortality of female breast and five gynecological cancers from various regions and countries were extracted from the GLOBOCAN 2022 database. We compared the proportion of total cases or deaths for cancers affecting female breast and five gynecological cancers and other tumor types in China and globally. Correlation analysis was conducted to evaluate the relationship between age-standardized incidence rate (ASIR) or age-standardized mortality rate (ASMR) and the Human Development Index (HDI). Additionally, age-specific rate curves were plotted for ten exemplary countries with different income levels. Results:. Female breast and five gynecological cancers in China accounted for 30.2% of all newly diagnosed cancer cases. Breast cancer and cervical cancer are the most commonly diagnosed, with nearly 507,000 new cases, representing 23.48% of the new cases. The incidence rates of breast, uterine corpus, ovarian, and vulvar cancers were positively associated with HDI tiers. Chinese women aged 50– 54 years are experiencing high incidence rates of breast, cervix uteri, corpus uteri, and ovarian cancers. Conclusions:. Female breast and five gynecological cancers continue to be a significant health concern for women in China and worldwide. It is crucial to implement comprehensive prevention strategies tailored to address the increasing trend among younger individuals and reduce regional disparities.

Abstract Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson’s disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+), respectively. Ferroptosis was identified by assessing the levels of Fe2+, ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models. Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe2+, ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro, myricetin treatment restored SH-SY5Y cell viability and alleviated MPP+-induced SH-SY5Y cell ferroptosis. Mechanistically, myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP+-treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD.

ObjectivesThe competency of radiology directly affects the quality and equity of medical services. Due to their different occupational characteristics compared to other specialists, this study aims to evaluate the impacts of lifestyles on competency and burnout in radiology residents in China.Materials and methodsA nationwide, cross-sectional survey was conducted from December 1, 2020 to April 30, 2021. A total of 12,208 radiology residents during their standardized residency training in China were invited. Multivariate linear regression and logistic regression were conducted to identify perceived competency and burnout associated with lifestyles.ResultsOf the 3,666 participants, 58.02% were female, 82.24% were aged

Struma ovarii (SO) represents a rare subset of ovarian germ cell tumors, with approximately 5% transforming into malignant SO (MSO). This study retrospectively analyzed clinical data from 23 SO patients treated at the Cancer Hospital of the Chinese Academy of Medical Sciences between January 2013 and December 2023, including 17 benign SO (BSO) and 6 MSO cases. Additionally, a systematic review of 164 cases of MSO confined to the ovary, reported in the literature from 1946 to 2024, was conducted. Data on pathological type, treatment, and prognosis were extracted, and univariate and multivariate Cox regression analyses were performed to identify risk factors for recurrence in stage I MSO. The median age at diagnosis was higher for BSO compared to MSO (58 vs. 42.5 years), with 70.6% of patients being postmenopausal. BSO commonly presented with abdominal distension or mass, with more than half having ascites, while MSO patients were asymptomatic and lacked ascites. Cox regression analyses revealed that ovarian cystectomy was adversely associated with recurrence risk in stage I MSO, likely due to surgically induced capsular rent and potential tumor spillage. Significantly lower recurrence risks were observed in patients who underwent unilateral or bilateral salpingo-oophorectomy (HR = 0.36, P = 0.019; HR = 0.19, P = 0.004, respectively). This study highlights the importance of the surgical approach in the management of stage I MSO. A thorough preoperative discussion of the benefits and risks of different surgical approaches is recommended for patients desiring fertility preservation. Postoperative adjuvant therapy has not been shown to have a significant impact on prognosis. For the treatment of recurrent MSO, selecting appropriate surgical and adjuvant therapeutic strategies is essential to improve the long-term prognosis of MSO patients.

Citrinin (CTN) has been reported to induce renal failure and structural damage, but its nephrotoxic effects and mechanisms are not fully understood. Therefore, we established a model by orally administering CTN (0, 1.25, 5, or 20 mg/kg) to mice for 21 consecutive days. Histological and biochemical analyses revealed that CTN caused structural damage to renal tubules, increased inflammatory cell infiltration, and elevated levels of serum markers of renal function (creatinine, urea, and uric acid). Moreover, mRNA transcript levels of the inflammatory factors TNF-α, IL-1β, and IL-6 were increased, indicating the occurrence of an inflammatory response. Furthermore, exposure to CTN induced renal oxidative stress by decreasing antioxidant GSH levels, antioxidant enzyme (SOD, CAT) activities, and increasing oxidative products (ROS, MDA). In addition, CTN increased the expression of proteins associated with endoplasmic reticulum (ER)stress and apoptotic pathways. ER stress has been shown to be involved in regulating various models of kidney disease, but its role in CTN-induced renal injury has not been reported. We found that pretreatment with the ER stress inhibitor 4-PBA (240 mg/kg, ip) alleviated CTN-induced oxidative stress, NF-κB pathway mediated inflammatory response, and apoptosis. Interestingly, 4-PBA also partially alleviated renal structural damage and dysfunction. Thus, ER stress may be a novel target for the prevention and treatment of CTN-induced renal injury.

Citrinin (CTN) is a mycotoxin commonly found in contaminated foods and feed, posing health risks to both humans and animals. However, the mechanism by which CTN damages the intestine remains unclear. In this study, a model of intestinal injury was induced by administering 1.25 mg/kg and 5 mg/kg of CTN via gavage for 28 consecutive days in 6-week-old Kunming mice, aiming to explore the potential mechanisms underlying intestinal injury. The results demonstrate that CTN can cause structural damage to the mouse jejunum. Additionally, CTN reduces the protein expression of Claudin-1, Occludin, ZO-1, and MUC2, thereby disrupting the physical and chemical barriers of the intestine. Furthermore, exposure to CTN alters the structure of the intestinal microbiota in mice, thus compromising the intestinal microbial barrier. Meanwhile, the results showed that CTN exposure could induce excessive apoptosis in intestinal cells by altering the expression of proteins such as CHOP and GRP78 in the endoplasmic reticulum and Bax and Cyt c in mitochondria. The mitochondria and endoplasmic reticulum are connected through the mitochondria-associated endoplasmic reticulum membrane (MAM), which regulates the membrane. We found that the expression of bridging proteins Fis1 and BAP31 on the membrane was increased after CTN treatment, which would exacerbate the endoplasmic reticulum dysfunction, and could activate proteins such as Caspase-8 and Bid, thus further inducing apoptosis via the mitochondrial pathway. Taken together, these results suggest that CTN exposure can cause intestinal damage by disrupting the intestinal barrier and inducing excessive apoptosis in intestinal cells.

Abstract Furin primarily localizes to the trans‐Golgi network (TGN), where it cleaves and activates a broad range of immature proproteins that play critical roles in cellular homeostasis, disease progression, and infection. Furin is retrieved from endosomes to the TGN after being phosphorylated, but it is still unclear how furin exits the TGN to initiate the post‐Golgi trafficking and how its activity is regulated in the TGN. Here three membrane‐associated RING‐CH finger (MARCHF) proteins (2, 8, 9) are identified as furin E3 ubiquitin ligases, which catalyze furin K33‐polyubiquitination. Polyubiquitination prevents furin from maturation by blocking its ectodomain cleavage inside cells but promotes its egress from the TGN and shedding. Further ubiquitin‐specific protease 32 (USP32) is identified as the furin deubiquitinase in the TGN that counteracts the MARCHF inhibitory activity on furin. Thus, the furin post‐Golgi trafficking is regulated by an interplay between polyubiquitination and phosphorylation. Polyubiquitination is required for furin anterograde transport but inhibits its proprotein convertase activity, and phosphorylation is required for furin retrograde transport to produce fully active furin inside cells.

As underground mining operations gradually extend deeper, the conditions for orebody occurrence become increasingly complex, and various geological disasters occur frequently. Rock masses are prone to different degrees and types of damage, making it impractical to continue using intact rock as a reference. To study the dynamic mechanical properties of damaged rock under actual conditions, this study subjected granite samples to impact and high-temperature damage. Detailed observations were made of the samples' surface morphology and microstructure before and after damage, and the patterns of damage changes were investigated. Subsequently, uniaxial compression tests at different loading rates were conducted on the damaged samples. By calculating the loading rate effect sensitivity, it was found that as the damage increased, the rate effect gradually diminished. In addition, this study also summarized the influence of damage and loading rate on the macroscopic failure characteristics of the samples. The novelty of this study lies in focusing on damaged rock, which more closely resembles the actual rock conditions encountered in most underground mining operations today. This research can provide a reference for stability assessment and safe construction in deep mining rock engineering and offers important insights into the feasibility of non-explosive extraction of damaged rock.

T-2 toxin, a mycotoxin found in foods and feeds, poses a threat to female reproductive health in both humans and animals. LncRNA CUFF.253988.1 (CUFF.253988.1), highly expressed in pigs, has an undisclosed regulatory role. This study aimed to establish a model of T-2 toxin-induced ovarian injury in sows, both in vivo and in vitro, and to explore the regulatory role and potential mechanisms of CUFF.253988.1. The results showed that feeding T-2 toxin-contaminated feed (1 mg/kg) induced ovarian follicle atresia and mitochondrial structural damage, accompanied by a significant upregulation of CUFF.253988.1 expression in the ovaries. Additionally, T-2 toxin inhibited the SIRT3/PGC1-α pathway associated with mitochondrial function. Moreover, T-2 toxin induced cell apoptosis by upregulating the expression of Cyt c, Bax, cleaved-caspase-9, and cleaved-caspase-3 proteins. In T-2 toxin-induced injury to the ovarian granulosa AVG-16 cells at concentrations of 10, 40 and 160 nM, not only were the previously mentioned effects observed, but also a decrease in mitochondrial membrane potential, ATP content, and an elevation in ROS levels. However, downregulating CUFF.253988.1 reversed T-2 toxin's inhibition of the SIRT3/PGC1-α pathway, alleviating mitochondrial dysfunction and reducing cell apoptosis. Notably, this may be attributed to the inhibition of T-2 toxin-induced enrichment of CUFF.253988.1 in mitochondria. In conclusion, CUFF.253988.1 plays a pivotal role in T-2 toxin-induced ovarian damage, operating through the inhibition of the SIRT3/PGC1-α pathway and promotion of cell apoptosis.

Background: While suboptimal medication adherence remains an obstacle to the management of hypertension and diabetes in China, few studies have investigated associated factors with medication adherence on different dimensions simultaneously. Objective: To systematically examine associated patient, family, and community factors with suboptimal medication adherence among people with hypertension and/or type 2 diabetes in China. Methods: The study stratified a random sample of 622 adults aged 45 years or older with hypertension and/or type 2 diabetes from three southeast cities in China in 2019. Trained interviewers used the Morisky Green Levine Medication Adherence Scale, Self-Efficacy to Manage Chronic Disease (SEMCD) Scale, and the Family Adaptability, Partnership, Growth, Affection, and Resolve (APGAR) Scale to assess medication adherence, self-efficacy, and family function, respectively. Participants also reported their perceived satisfaction with community health services (quantity, quality, affordability, and overall acceptance). The study used the multivariable logistic regression to assess the association of patient, family, and community factors with suboptimal medication adherence. Results: Among the participants, 42.9% reported suboptimal medication adherence. In the multivariable logistic regression model, male participants (odds ratio [OR] = 0.55, p = 0.001) had higher medication adherence compared to females. Having a self-efficacy score that was lower than or equal to the sample mean was significantly associated with lower adherence (OR = 1.44, p = 0.039). Participants unsatisfied with the affordability of community health services and medicine had lower adherence (OR = 2.18, p = 0.028) than those neutral or satisfied. There were no significant associations between family function and medication adherence. Conclusions: Sex, self-efficacy, and perceived affordability of community health services were important factors associated with medication adherence. Healthcare professionals are recommended to consider multiple factors and leverage services and resources in community health centers when promoting medication adherence.

Abstract Nanopore direct RNA sequencing (DRS) has emerged as a powerful tool for RNA modification identification. However, concurrently detecting multiple types of modifications in a single DRS sample remains a challenge. Here, we develop TandemMod, a transferable deep learning framework capable of detecting multiple types of RNA modifications in single DRS data. To train high-performance TandemMod models, we generate in vitro epitranscriptome datasets from cDNA libraries, containing thousands of transcripts labeled with various types of RNA modifications. We validate the performance of TandemMod on both in vitro transcripts and in vivo human cell lines, confirming its high accuracy for profiling m6A and m5C modification sites. Furthermore, we perform transfer learning for identifying other modifications such as m7G, Ψ, and inosine, significantly reducing training data size and running time without compromising performance. Finally, we apply TandemMod to identify 3 types of RNA modifications in rice grown in different environments, demonstrating its applicability across species and conditions. In summary, we provide a resource with ground-truth labels that can serve as benchmark datasets for nanopore-based modification identification methods, and TandemMod for identifying diverse RNA modifications using a single DRS sample.

Abstract In this scoping review, we evaluated the performance of artificial intelligence (AI) in clinical radiology practice and examined health professionals' perspectives regarding AI use in radiology. This review followed the Joanna Briggs Institute (JBI) methodological guidelines. We searched multiple databases and the gray literature from March 15, 2016 to December 31, 2023. Of 49 articles reviewed, 13 assessed the performance of AI in radiology clinical practice, and 36 examined the attitudes of health professionals toward the use of AI in radiology. In four separate studies, AI significantly improved the diagnostic sensitivity or detection rate. Furthermore, six articles emphasized a significant reduction in case reading times with AI use. Although three studies suggested an increase in specificity with the assistance of AI, these findings did not reach statistical significance. Health professionals expressed the belief that AI would have a significant impact on radiology but would not replace radiologists in the near future. Limited knowledge of AI was observed among health professionals, who supported increased education and explicit regulations and guidelines related to AI. Overall, AI can enhance diagnostic efficiency and accuracy in clinical radiology practice. However, knowledge gaps and the concerns of health professionals should be addressed by prioritizing education and reinforcing ethical and legal regulations to facilitate the advancement of AI use in radiology. This scoping review provides evidence toward a comprehensive understanding of AI's potential in clinical radiology practice, promoting its use and stimulating further discussion on related challenges and implications.

Abstract Internal N6-methyladenosine (m6A) modifications are among the most abundant modifications of messenger RNA, playing a critical role in diverse biological and pathological processes. However, the functional role and regulatory mechanism of m6A modifications in the immune response to Mycobacterium tuberculosis infection remains unknown. Here, we report that methyltransferase-like 14 (METTL14)-dependent m6A methylation of NAPDH oxidase 2 (Nox2) mRNA was crucial for the host immune defense against M. tuberculosis infection and that M. tuberculosis-secreted antigen EsxB (Rv3874) inhibited METTL14-dependent m6A methylation of Nox2 mRNA. Mechanistically, EsxB interacted with p38 MAP kinase and disrupted the association of TAB1 with p38, thus inhibiting the TAB1-mediated autophosphorylation of p38. Interaction of EsxB with p38 also impeded the binding of p38 with METTL14, thereby inhibiting the p38-mediated phosphorylation of METTL14 at Thr72. Inhibition of p38 by EsxB restrained liquid–liquid phase separation (LLPS) of METTL14 and its subsequent interaction with METTL3, preventing the m6A modification of Nox2 mRNA and its association with the m6A-binding protein IGF2BP1 to destabilize Nox2 mRNA, reduce ROS levels, and increase intracellular survival of M. tuberculosis. Moreover, deletion or mutation of the phosphorylation site on METTL14 impaired the inhibition of ROS level by EsxB and increased bacterial burden or histological damage in the lungs during infection in mice. These findings identify a previously unknown mechanism that M. tuberculosis employs to suppress host immunity, providing insights that may empower the development of effective immunomodulators that target M. tuberculosis.

Abstract Radioiodine capture from nuclear fuel waste and contaminated water sources is of enormous environmental importance, but remains technically challenging. Herein, we demonstrate robust covalent organic frameworks (COFs) with antiparallel stacked structures, excellent radiation resistance, and high binding affinities toward I2, CH3I, and I3 − under various conditions. A neutral framework (ACOF-1) achieves a high affinity through the cooperative functions of pyridine-N and hydrazine groups from antiparallel stacking layers, resulting in a high capacity of ~2.16 g/g for I2 and ~0.74 g/g for CH3I at 25 °C under dynamic adsorption conditions. Subsequently, post-synthetic methylation of ACOF-1 converted pyridine-N sites to cationic pyridinium moieties, yielding a cationic framework (namely ACOF-1R) with enhanced capacity for triiodide ion capture from contaminated water. ACOF-1R can rapidly decontaminate iodine polluted groundwater to drinking levels with a high uptake capacity of ~4.46 g/g established through column breakthrough tests. The cooperative functions of specific binding moieties make ACOF-1 and ACOF-1R promising adsorbents for radioiodine pollutants treatment under practical conditions.

AbstractIncrease of regulatory T cells (Tregs) in the tumour microenvironment predicts worse survival of patients with various types of cancer. Recently, B cells play a significant role in the maintenance of Treg cells. However, the relevance of regulatory B cells (Bregs) to tumour immunity in humans remains elusive. Flow cytometry analysis was used to detect the Bregs and Tregs. Double staining results illustrated that the proportion of Bregs and Tregs were prominently higher in cervical cancer than normal tissues. Increase of Bregs and Tregs in cervical cancer microenvironment was associated with poor survival. Furthermore, Bregs cocultured with cervical cancer cell lines increased and induced Tregs. To sum up, the increased expression of Bregs contributes to the differentiation of CD4+ T cells into Tregs in the cervical cancer.

Drawing upon data from the 2018 CHARLS, this paper utilizes MEPI and a 10% threshold indicator to, respectively, assess the energy poverty (EP) status among middle-aged and older adults in China, focusing on the unavailability and unaffordability of energy services. Additionally, an econometric model is constructed to investigate the effects of EP on the health and welfare of middle-aged and older adults. Regression results indicate that EP exerts a significant negative impact on the health and welfare of middle-aged and older adults. This conclusion remains robust after conducting endogeneity and robustness tests, demonstrating its validity. Finally, based on the calculation results, we propose relevant policy recommendations including enhancing energy services for older adults in rural areas, integrating household energy alternatives with targeted poverty alleviation, enhancing monitoring mechanisms, and conducting energy education activities to alleviate EP and improve the quality of life of middle-aged and older adults.

Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer with a poor prognosis that often shows resistance to chemotherapy. This study retrospectively analyzed 247 patients with OCCC who were admitted to the Cancer Hospital of the Chinese Academy of Medical Sciences (CAMS) between August 2007 and August 2023. Univariate and multivariate Cox regression analyses were used to identify clinicopathological factors associated with OCCC, and a nomogram prediction model was developed to predict OCCC patient survival outcomes. Kaplan‒Meier survival analysis was used to compare survival outcomes among patients with recurrent disease. Compared with systemic therapy, secondary debulking surgery significantly improved the postrecurrence survival (PRS) rate (P = 0.006). Subgroup analysis revealed that the survival benefit was more pronounced in patients with recurrence and satisfactory tumor shrinkage (PPRS = 0.01, PPFS2 = 0.047). The multivariate analysis revealed that positive preoperative ascites, incomplete remission following initial treatment, and undergoing more than six cycles of postoperative chemotherapy were independent prognostic factors affecting overall survival (OS). Additionally, patients with a positive PD-L1 test who received immunotherapy did not experience relapse during the follow-up period. In conclusion, the secondary clearance procedure offers significant benefits for patients with recurrent OCCC, and patients may experience a survival benefit from supplemental immune or targeted therapy at the end of chemotherapy. The development of a personalized treatment plan can help achieve precise treatment, improve prognosis, and enhance patients' quality of life.

Diabetic wounds are serious clinical complications which manifest wet condition due to the mass exudate, along with disturbed regulation of inflammation, severe oxidative stress and repetitive bacterial infection. Existing treatments for diabetic wounds remain unsatisfactory due to the lack of ideal dressings that encompass mechanical performance, adherence to moist tissue surfaces, quick repair, and diverse therapeutic benefits. Herein, we fabricated a wet adhesive, self-healing, glucose-responsive drug releasing hydrogel with efficient antimicrobial and pro-healing properties for diabetic wound treatment. PAE hydrogel was constructed with poly(acrylic acid-co-acrylamide) (AA-Am) integrated with a dynamic E-F crosslinker, which consisted of epigallocatechin gallate (EGCG) and 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA). Due to the dynamic crosslinking nature of boronate esters, abundant catechol groups and hydrogen bonding, PAE hydrogel demonstrated excellent mechanical properties with about 1000 % elongation, robust adhesion to moist tissues, fast self-healing, and absorption of biofluids of 10 times of its own weight. Importantly, PAE hydrogel exhibited sustained and glucose-responsive release of EGCG. Together, the bioactive PAE hydrogel had effective antibacterial, antioxidative, and anti-inflammatory properties in vitro, and accelerated diabetic wound healing in rats via reducing tissue-inflammatory response, enhancing angiogenesis, and reprogramming of macrophages. Overall, this versatile hydrogel provides a straightforward solution for the treatment of diabetic wound, and shows potential for other wound-related application scenarios.

Efficient UAV tracking faces challenges due to limited onboard resources, short battery life, and payload constraints. Discriminative correlation filters (DCF)-based trackers have traditionally been preferred for their efficiency. However, recent lightweight deep learning (DL)-based trackers, leveraging model compression, exhibit significant CPU efficiency and precision. Unfortunately, existing model compression approaches have struggled with maintaining tracking precision, especially at higher compression rates. This paper addresses this limitation with a novel approach, called disentangled representation learning with mutual information maximization (DR-MIM). DR-MIM has the potential to enhance the accuracy and efficiency of DL-based trackers, particularly in UAV tracking. The primary concept underpinning this approach is disentangled representation which bifurcates the feature space into two distinct categories: identity-related and identity-unrelated elements. This bifurcation serves as a critical component, powering the heightened level of precision and efficiency attained by DL-based trackers. The focus of this work is predominantly on the employment of exclusively identity-related features. As a result of this focus, there’s a noticeable escalation in the efficacy of the feature representation. To further enhance efficiency without compromising accuracy, the network has been quantified and named DR-MIM (v2). Exhaustive experiments conducted across four aerial tracking benchmarks have demonstrated the superiority of the proposed method. A standout performance on VisDrone2018 showcases DR-MIM (v2)’s impressive GPU speed of 658 FPS, coupled with a maintained precision of 82.1%, underscoring the potential of proposed approach in real-world UAV tracking scenarios.

Chaperone-mediated autophagy is one of three types of autophagy and is characterized by the selective degradation of proteins. Chaperone-mediated autophagy contributes to energy balance and helps maintain cellular homeostasis, while providing nutrients and support for cell survival. Chaperone-mediated autophagy activity can be detected in almost all cells, including neurons. Owing to the extreme sensitivity of neurons to their environmental changes, maintaining neuronal homeostasis is critical for neuronal growth and survival. Chaperone-mediated autophagy dysfunction is closely related to central nervous system diseases. It has been shown that neuronal damage and cell death are accompanied by chaperone-mediated autophagy dysfunction. Under certain conditions, regulation of chaperone-mediated autophagy activity attenuates neurotoxicity. In this paper, we review the changes in chaperone-mediated autophagy in neurodegenerative diseases, brain injury, glioma, and autoimmune diseases. We also summarize the most recent research progress on chaperone-mediated autophagy regulation and discuss the potential of chaperone-mediated autophagy as a therapeutic target for central nervous system diseases.

Abstract Drug nanoaggregates are particles that can deleteriously cause false positive results during drug screening efforts, but alternatively, they may be used to improve pharmacokinetics when developed for drug delivery purposes. The structural features of molecules that drive nanoaggregate formation remain elusive, however, and the prediction of intracellular aggregation and rational design of nanoaggregate-based carriers are still challenging. We investigate nanoaggregate self-assembly mechanisms using small molecule fragments to identify the critical molecular forces that contribute to self-assembly. We find that aromatic groups and hydrogen bond acceptors/donors are essential for nanoaggregate formation, suggesting that both π-π stacking and hydrogen bonding are drivers of nanoaggregation. We apply structure-assembly-relationship analysis to the drug sorafenib and discover that nanoaggregate formation can be predicted entirely using drug fragment substructures. We also find that drug nanoaggregates are stabilized in an amorphous core-shell structure. These findings demonstrate that rational design can address intracellular aggregation and pharmacologic/delivery challenges in conventional and fragment-based drug development processes.

Abstract Background Genomic testing transforms the diagnosis and management of rare conditions. However, uncertainty exists on how to best measure genomic outcomes for informing healthcare priorities. Using the HTA-preferred method should be the starting point to improve the evidence-base. This study explores the responsiveness of SF-6D, EQ-5D-5L and AQoL-8D following genomic testing across childhood and adult-onset genetic conditions. Method Self-reported patient-reported outcomes (PRO) were obtained from: primary caregivers of children with suspected neurodevelopmental disorders (NDs) or genetic kidney diseases (GKDs) (carers’ own PRO), adults with suspected GKDs using SF-12v2; adults with suspected complex neurological disorders (CNDs) using EQ-5D-5L; and adults with dilated cardiomyopathy (DCM) using AQol-8D. Responsiveness was assessed using the standardised response mean effect-size based on diagnostic (having a confirmed genomic diagnosis), personal (usefulness of genomic information to individuals or families), and clinical (clinical usefulness of genomic information) utility anchors. Results In total, 254 people completed PRO measures before genomic testing and after receiving results. For diagnostic utility, a nearly moderate positive effect size was identified by the AQoL-8D in adult DCM patients. Declines in physical health domains masked any improvements in mental or psychosocial domains in parents of children affected by NDs and adult CNDs and DCM patients with confirmed diagnosis. However, the magnitude of the changes was small and we did not find statistically significant evidence of these changes. No other responsiveness evidence related to diagnostic, clinical, and personal utility of genomic testing was identified. Conclusion Generic PRO measures may lack responsiveness to the diagnostic, clinical and personal outcomes of genomics, but further research is needed to establish their measurement properties and relevant evaluative space in the context of rare conditions. Expected declines in the physical health of people experiencing rare conditions may further challenge the conventional application of quality of life assessments.

This paper studies an artificial neural network (ANN) for multi-asset European options. Firstly, a simple three-layer ANN-3 is established with undetermined weights and bias. Secondly, the time–space discrete PDE of the multi-asset option is given and the corresponding discrete data are fed into the ANN-3. Then, using least squares error as the objective function, the weights and bias of ANN-3 are trained well. Numerical examples are carried out to confirm the stability, accuracy and efficiency. Experiments show the ANN’s relative error is about 0.8%. This method can be extended into multi-layer ANN-q(q>3) and extended into American options.

The effectiveness of removing lymph nodes before initial treatment in patients with locally advanced cervical cancer is still debated. This article presents a meta-analysis that systematically evaluates the impact of this approach on oncological outcomes. A systematic literature search of PubMed, Embase, Science Direct, and the Cochrane Database of Systematic Reviews (up to December 2023) was performed to obtain relevant studies. The findings were combined using fixed-effects models to address potential differences. Combined risk ratios (HR) and 95% confidence intervals (CI) were calculated. Egger's test was used to assess publication bias. Out of 1025 screened articles, four studies (involving 838 women) met the inclusion criteria. The results showed that lymph node dissection before initial treatment did not affect overall survival (OS) in patients with locally advanced cervical cancer compared to concurrent radiotherapy (HR = 1.11, 95% CI = 0.91-1.36, P = 0.30). It also did not increase the incidence of postoperative complications or cause delays in radiotherapy. In particular, removing larger lymph nodes (>2cm) aided in defining the radiation field and decreasing radiotherapy-related complications. The surgical technique also had some impact on postoperative complications. In summary, in order to obtain the best therapeutic outcomes, personalized plans should be developed for each patient, accounting for their individual circumstances to achieve precise treatment and enhance their quality of life.

BackgroundThe association between body mass index (BMI) and rapid eye-movement (REM) sleep-related behavioral disorder (RBD) in Parkinson’s disease (PD) remains unknown. Our study was to investigate the association of BMI with RBD in PD patients.MethodsIn this cross-sectional study, a total of 1,115 PD participants were enrolled from Parkinson’s Progression Markers Initiative (PPMI) database. BMI was calculated as weight divided by height squared. RBD was defined as the RBD questionnaire (RBDSQ) score with the cutoff of 5 or more assessed. Univariable and multivariable logistic regression models were performed to examine the associations between BMI and the prevalence of RBD. Non-linear correlations were explored with use of restricted cubic spline (RCS) analysis. And the inflection point was determined by the two-line piecewise linear models.ResultsWe identified 426 (38.2%) RBD. The proportion of underweight, normal, overweight and obese was 2.61, 36.59, 40.36, and 20.44%, respectively. In the multivariate logistic regression model with full adjustment for confounding variables, obese individuals had an odds ratio of 1.77 (95% confidence interval: 1.21 to 2.59) with RBD compared with those of normal weight. In the RCS models with three knots, BMI showed a non-linear association with RBD. The turning points of BMI estimated from piecewise linear models were of 28.16 kg/m2, 28.10 kg/m2, and 28.23 kg/m2 derived from univariable and multivariable adjusted logistic regression models. The effect modification by depression on the association between BMI and RBD in PD was also found in this study. Furthermore, the sensitivity analyses linked with cognition, education, and ethnic groups indicated the robustness of our results.ConclusionThe current study found a significant dose–response association between BMI and RBD with a depression-based difference in the impact of BMI on RBD in PD patients.

Myostatin (Mstn) was reported to be involved in multiple biological processes including the regulation of skeletal muscle growth, lipid metabolism and reproduction in vertebrates, therefore, it might play an essential role in the fine balance between growth and reproduction. In order to clarify the roles of Mstn in fish reproduction, we systematically investigated the gonadal development and fertility of mstnb mutants in Nile tilapia (Orochromis niloticus). In the present study, mstnb was found to be expressed in the different cell types of gonads by fluorescence in situ hybridization (FISH). Mutation of mstnb resulted in excessive proliferation of phase II follicles in the ovaries while the numbers of phase III follicles were significantly reduced at 210 days after hatching (dah). Interestingly, significant decline of cyp19a1a gene expression, the serum 17β-estradiol (E2), vitellogenin (VTG) were detected at 210 dah. At 360 dah, the ovarian development of mstnb-/- XX tilapia was partially recovered and female fish spawn regularly, however, they were subfertile and produced the poor-quality eggs with significantly lower offspring survival rate. The dramatic up-regulation of cyp19a1a gene expression and serum E2 level at 360 dah might account for the recovery of ovarian development. In mstnb-/- males, excessive proliferation of spermatogonia and retardation of testicular differentiation were found throughout the whole development stages. In mstnb-/- males, evident declines of gonadosomatic index (GSI), cyp11b2 gene expression, and 11-Ketotestosterone (11-KT) were detected at 210 dah, while the mRNA level of cyp11b2 and serum 11-KT level were significantly upregulated at 360 dah. However, mstnb-/- males were infertile since mutation of mstnb gene led to excessive increase of apoptosis of testicular cells and spermiation obstacle. Taken together, these results indicated that Mstn might be an essential regulator for the maintenance of fish fertility.

Osteoarthritis (OA) is a degenerative joint disease, Increasingly, mitochondrial autophagy has been found to play an important regulatory role in the prevention and treatment of osteoarthritis. Koumine is a bioactive alkaloid extracted from the plant Gelsemium elegans. In previous research, Koumine was found to have potential in improving the progression of OA in rats. However, the specific mechanism of its action has not been fully explained. Therefore, the aim of this study was to investigate whether Koumine can alleviate OA in rats by influencing mitochondrial autophagy. In the in vitro study, rat chondrocytes (RCCS-1) were induced with IL-1β (10 ng/mL) to induce inflammation, and Koumine (50 μg/mL) was co-treated. In the in vivo study, a rat OA model was established by intra-articular injection of 2% papain, and Koumine was administered orally (1 mg/kg, once daily for two weeks). It was found that Koumine effectively reduced cartilage erosion in rats with osteoarthritis. Additionally, it decreased the levels of inflammatory factors such as IL-1β, IL-6, and extracellular matrix (ECM) components MMP13 and ADAMTS5 in chondrocytes and articular cartilage tissue, while increasing the level of Collagen II.Koumine inhibited the production of reactive oxygen species (ROS) in cartilage tissue and increased the number of autophagosomes in chondrocytes and articular cartilage tissue. Additionally, it upregulated the expression of mitochondrial autophagy proteins LC3Ⅱ/Ⅰ, PINK1, Parkin, and Drp1. The administration of Mdivi-1 (50 μM) reversed the enhanced effect of Koumine on mitochondrial autophagy, as well as its anti-inflammatory and anti-ECM degradation effects in rats with OA. These findings suggest that Koumine can alleviate chondrocyte inflammation and improve the progression of OA in rats by activating PINK1/Parkin-mediated mitochondrial autophagy.

ABSTRACTBumblebees are among the most abundant and important pollinators for sub-alpine and alpine flowering plant species in the Northern Hemisphere, but little is known about their adaptations to high elevations. In this article, we focused on two bumblebee species, Bombus friseanus and Bombus prshewalskyi, and their respective gut microbiota. The two species, distributed through the Hengduan Mountains of southwestern China, show species replacement at different elevations. We performed genome sequencing based on 20 worker bee samples of each species. Applying evolutionary population genetics and metagenomic approaches, we detected genes under selection and analyzed functional pathways between bumblebees and their gut microbes. We found clear genetic differentiation between the two host species and significant differences in their microbiota. Species replacement occurred in both hosts and their bacteria (Snodgrassella) with an increase in elevation. These extremely high-elevation bumblebees show evidence of positive selection related to diverse biological processes. Positively selected genes involved in host immune systems probably contributed to gut microbiota changes, while the butyrate generated by gut microbiota may influence both host energy metabolism and immune systems. This suggests a close association between the genomes of the host species and their microbiomes based on some degree of natural selection.IMPORTANCETwo closely related and dominant bumblebee species, distributed at different elevations through the Hengduan Mountains of southwestern China, showed a clear genomic signature of adaptation to elevation at the molecular level and significant differences in their respective microbiota. Species replacement occurred in both hosts and their bacteria (Snodgrassella) with an increase in elevation. Bumblebees’ adaptations to higher elevations are closely associated with their gut microbiota through two biological processes: energy metabolism and immune response. Information allowing us to understand the adaptive mechanisms of species to extreme conditions is implicit if we are to conserve them as their environments change.

Introduction:Dental pulp stem cells from humans possess self-renewal and versatile differentiation abilities. These cells, known as DPSC, are promising for tissue engineering due to their outstanding biological characteristics and ease of access without significant donor site trauma. Existing methods for isolating DPSC mainly include enzyme digestion and explant techniques. Compared with the enzymatic digestion technique, the outgrowth method is less prone to cell damage and loss during the operation, which is essential for DPSC with fewer tissue sources.Methods:In order to maximize the amount of stem cells harvested while reducing the cost of DPSC culture, the feasibility of the optimized explant technique was evaluated in this experiment. Cell morphology, minimum cell emergence time, the total amount of cells harvested, cell survival, and proliferative and differentiation capacity of DPSC obtained with different numbers of explant attachments (A1-A5) were evaluated.Results:There was a reduction in the survival rate of the cells in groups A2-A5, and the amount of harvested DPSC decreased in A3-A5 groups, but the DPSC harvested in groups A1-A4 had similar proliferative and differentiation abilities. However, starting from group A5, the survival rate, proliferation and differentiation ability of DPSC decreased significantly, and the adipogenic trend of the cells became more apparent, indicating that the cells had begun to enter the senescence state.Discussion:The results of our study demonstrated that the DPSC obtained by the optimized explant method up to 4 times had reliable biological properties and is available for tissue engineering.

Abstract In recent years, the role of nobiletin in neuronal disorders has received extensive attention. However, the study of nobiletin in the peripheral nervous system is limited. Nobiletin, as a compound with high fat solubility, high bioavailability and low toxicity, has been extensively studied. Accumulating scientific evidence has shown that nobiletin has a variety of biological functions in the nervous system, such as inhibiting the expression of inflammatory factors, reducing the neurotoxic response, improving the antioxidant capacity, promoting the survival of nerve cells, promoting axon growth, reducing blood‒brain barrier permeability, reducing brain oedema, promoting cAMP response element binding protein expression, improving memory, and promoting mild depolarization of nerve cell mitochondria to improve antioxidative stress capacity. Accumulating studies have shown that nobiletin also protects enteric nervous system, spinal cord and sciatic nerve. To explore the new therapeutic potential of nobiletin in the nervous system, recent and relevant research progress is reviewed in this article. This will provide a new research idea for nobiletin in the nervous system.

The hot deformation behavior of AZ42 alloy was observed using thermal compression tests at a temperature scope of 250–400 °C and strain rate scope of 0.001–1 s−1. True stress-strain curves exhibited a combination of work hardening and dynamic softening features. A Northern Goshawk algorithm (NGO)-optimized artificial neural network (ANN) model was proposed. The established NGO-ANN model demonstrated impressive prediction accuracy, achieving a high determination coefficient of 0.991, a mean absolute percentage error of 3.51 %, and a root mean square error of 2.73. Subsequently, three-dimensional (3D) hot processing map based on the dynamic material model (DMM) theory was created. There were three different regions within the processing maps: the flow instability region (region A: 250–260 °C, 0.02–1 s−1, and region B: 300–400 °C, 0.01–0.1 s−1), high-power dissipation coefficient region (region C: 350–400 °C, 0.001–0.02 s−1, and region D: 300–350 °C, 0.5–1 s−1), and low power dissipation efficiency safety region (region E: the rest ones). Microstructural analysis revealed significant local plastic flow features in the flow instability region and a combination of coarse initial deformation grains and fine dynamic recrystallization (DRX) grains in the low power dissipation efficiency safety region. Fine and uniform grains were observed in the high-power dissipation efficiency region with DRX degree VDRX as high as 85.6 %, resulting in the best mechanical properties. Based on the established 3D hot processing map, the optimal process domains were determined.

With the discovery of the pivotal role of macrophages in tissue regeneration through shaping the tissue immune microenvironment, various immunomodulatory strategies have been proposed to modify traditional biomaterials. Decellularized extracellular matrix (dECM) has been extensively used in the clinical treatment of tissue injury due to its favorable biocompatibility and similarity to the native tissue environment. However, most reported decellularization protocols may cause damage to the native structure of dECM, which undermines its inherent advantages and potential clinical applications. Here, we introduce a mechanically tunable dECM prepared by optimizing the freeze-thaw cycles. We demonstrated that the alteration in micromechanical properties of dECM resulting from the cyclic freeze-thaw process contributes to distinct macrophage-mediated host immune responses to the materials, which are recently recognized to play a pivotal role in determining the outcome of tissue regeneration. Our sequencing data further revealed that the immunomodulatory effect of dECM was induced via the mechnotrasduction pathways in macrophages. Next, we tested the dECM in a rat skin injury model and found an enhanced micromechanical property of dECM achieved with three freeze-thaw cycles significantly promoted the M2 polarization of macrophages, leading to superior wound healing. These findings suggest that the immunomodulatory property of dECM can be efficiently manipulated by tailoring its inherent micromechanical properties during the decellularization process. Therefore, our mechanics-immunomodulation-based strategy provides new insights into the development of advanced biomaterials for wound healing.

Abstract Autonomic symptoms (AS) are critical in Parkinson’s disease (PD). We aimed to determine the relative significance of clinical factors allowing predictions about incidence of AS, and examine AS profiles among PD patients by motor subtype and its relation to AS. The cross-sectional data of a multicentre sample, including 714 PD patients and 194 healthy controls from Parkinson’s Progression Marker Initiative study and Pingchan granule study were analyzed, stratified by PD subtypes [postural instability and gait disturbances (PIGD), tremor dominant (TD), and indeterminate] and domain autonomic dysfunction. Compared with healthy controls, PD patients scored higher in the total Scales for Outcomes in Parkinson's Disease-Autonomic dysfunction score and in several domain scores in particular, and there was a significant overlap in domain AS. Risk factors of individual domain autonomic dysfunction were heterogeneous. PIGD and indeterminate were the predominant subtypes in pupillomotor and thermoregulatory symptoms. TD and indeterminate were more likely to suffer from cardiovascular problem. The odd in sexual dysfunction was significant for PIGD. Gastrointestinal and urinary symptoms seemed not to be associated with a specific subtype. Our study demonstrated that AS were highly heterogeneous and 3 subtypes differed in autonomic performance, providing clues to understand mechanisms underlying AS in PD.

Abstract Since the identification of the first case of pneumonia of unknown cause in 2019, the COVID‐19 pandemic has spread the globe for over 3 years. As the most populous country in the world, China's disease prevention policies and response plans concern the health of the country's 1.4 billion people and beyond. During the course of the pandemic, scientific research has been accumulated and given evidence‐based support to the official guidance of COVID‐19 management. The National Health Commission of China have compiled, published, and updated a total of 10 versions of the “Diagnosis and Treatment Protocol for COVID‐19 Patients” to better inform clinical practitioners and staff to effectively screen, diagnose, manage, treat, and care for cases of severe acute respiratory syndrome coronavirus 2 infection. This paper compares and summarizes each version of the protocol in terms of etiology and epidemiology, clinical manifestation and diagnosis, treatment and nursing, disease control and management, presenting detailed changes, additions, deletions, and refinement of the protocols.

Objective Cerebral infarction is the main cause of death in patients with cerebrovascular diseases. Our research aimed to screen and validate pyroptosis-related genes in cerebral infarction for the targeted therapy of cerebral infarction. Methods and results A total of 1,517 differentially expressed genes (DEGs) were obtained by DESeq2 software analysis. Gene set enrichment analysis results indicated that genes of middle cerebral artery occlusion (MCAO) mice aged 3 months and 18 months were enriched in pyroptosis, respectively. Differentially expressed pyroptosis-related genes (including Aim2, Casp8, Gsdmd, Naip2, Naip5, Naip6 and Trem2) were obtained through intersection of DEGs and genes from pyroptosis Gene Ontology Term (GO:0070269), and they were up-regulated in the brain tissues of MCAO mice in GSE137482. In addition, Casp8, Gsdmd, and Trem2 were verified to be significantly up-regulated in MCAO mice in GSE93376. The evaluation of neurologic function and triphenyltetrazolium chloride staining showed that the MCAO mouse models were successfully constructed. Meanwhile, the expressions of TNF-α, pyroptosis-related proteins, Casp8, Gsdmd and Trem2 in MCAO mice were significantly up-regulated. We selected Trem2 for subsequent functional analysis. OGD treatment of BV2 cell in vitro significantly upregulated the expressions of Trem2. Subsequent downregulation of Trem2 expression in OGD-BV2 cells further increased the level of pyroptosis. Therefore, Trem2 is a protective factor regulating pyroptosis, thus influencing the progression of cerebral infarction. Conclusions Casp8, Gsdmd and Trem2 can regulate pyroptosis, thus affecting cerebral infarction.

This paper develops a time-space double radial basis function (TSDRBF) method to solve PDEs arising from multiasset option pricing. By TSDRBF discretization for the high-dimensional PDEs, a linear system (LS) is obtained. After solving the LS, multi-asset options of European and American style are restored, with number N of space discretization, number M¯ of time nodes, and number M of time RBF discretization. Numerical examples confirm that the TSDRBF method has exponentially convergent rates for the number N and number M, while the convergence is linear for the number M¯. Compared with finite difference, TSDRBF avoids the difficulty of space discretization, and the convergence is greatly improved.

Background. Coronary artery disease (CAD) is a type of cardiovascular disease which is one of the leading causes of death around the world. The presence of coronary stenosis is considered a pivotal indicator in the diagnosis of various CADs. The main purpose of this paper was to investigate the feasibility of an anchor-free deep learning (DL) method, fully convolutional one-stage object detection (FCOS), in coronary artery stenosis automatic detection. Methods. First, 2786 invasive coronary angiography (ICA) images from 130 patients were randomly divided into training, validation, and testing datasets using the 10-fold cross-validation approach. Then, FCOS was compared with other three widely used anchor-based DL models: single shot multibox detector (SSD), faster region-based convolutional network (Faster R-CNN), and you only look once (YOLOv3), in terms of precision, recall, F1 score, average precision (AP), and average recall (AR). Finally, the performances of different models in the detection of stenosis were compared in either single or multiple lesion scenarios using statistical tests. Results. FCOS achieved significantly superior precision (96.14% ± 0.53%), recall (94.36% ± 0.79%), F1 score (95.22% ± 0.56%), AP0.50 (93.36% ± 0.93%), AR0.50:0.95 (64.73% ± 1.46%), APsmall (55.04 ± 0.96%), APmedium (59.97 ± 1.13%), and APlarge (68.09 ± 5.18%) compared to Faster R-CNN and YOLOv3. Moreover, FCOS demonstrated significantly higher AR0.50:0.95 and APsmall compared to SSD. Regardless of the presence of single or multiple coronary stenoses in ICA images, FCOS also outperformed Faster R-CNN and YOLOv3. Furthermore, it showed significantly higher AR0.50:0.95 compared to SSD when in the multiple stenosis scenario. Conclusions. It is feasible to use the anchor-free DL model FCOS in detecting coronary stenosis based on ICA images.

With heightened concern over carbon neutrality and increased energy market fluctuations against the backdrop of increasing global uncertainty, it becomes imperative to thoroughly investigate the information transmission and risk contagion between carbon and energy markets. This paper empirically explores the return and volatility connectedness among carbon and energy markets (electricity, natural gas, crude oil, and coal) from April 2008 to September 2021 by employing the time-frequency domain connectedness approaches. This paper indicates: i) the return connectedness exceeds volatility connectedness, and extreme events can intensify the dynamic changes; ii) the return connectedness is predominantly concentrated at high-frequency, while the volatility connectedness is concentrated at medium- and low-frequency. Net volatility connectedness maintains a consistent direction across all markets in the time-frequency domain. In contrast, net return connectedness exhibits an opposing direction at high-frequency and medium- and low-frequency. iii) the natural gas and coal markets predominantly act as net transmitters in both return and volatility connectedness, while the electricity, crude oil, and carbon markets operate as net receivers. Moreover, during the COVID-19 pandemic, the carbon market emerged as an information receiver in time-frequency domains and acted as a risk transmitter, exporting risk, particularly to the electricity market. These conclusions help investors, high-carbon enterprises, and policymakers to comprehensively understand the carbon-energy relationships, thereby supporting sustainable energy development and low-carbon economic goals. Simultaneously, this paper provides insights for enhancing carbon markets in emerging markets like China.

Fluorescent probes, typically based on the intramolecular charge transfer (ICT) mechanism, have received considerable research attention in cell detection due to their non-invasiveness, fast response, easy regulation, high sensitivity, and low damage tolerance for in vivo bio-samples. Generally, intracellular pH and biological species such as various gases, metal ions, and anions constitute the foundation of cells and participate in the basic physiological processes, whose abnormal level can lead to poisoning, cardiovascular disease, and cancer in living organisms. Therefore, monitoring of their quantity plays an essential role in understanding the status of organisms and preventing, diagnosing, and treating diseases. In the last decades, remarkable progress has been made in developing ICT probes for the detection of biological elements. In this review, we highlight the recent ICT probes focusing primarily on the detection of intracellular pH, various gases (H2S, CO, H2O2, and NO), metal ions (Cu2+, Hg2+, Pb2+, Zn2+, and Al3+), and anions (ClO−, CN−, SO32−, and F−). In addition, we discuss the issues and limitations of ICT-based fluorescent probes for in vivo detection and explore the clinical translational potential and challenges of these materials, providing valuable guidance and insights for the design of fluorescent materials.

As an important lever for China’s green development strategy, whether the new Environmental Protection Law can effectively form investment incentives for enterprises has attracted much attention and is also an important topic that theoretical research urgently needs to explore. This paper utilizes corporate data from non-financial listed companies in Shanghai and Shenzhen A-shares from 2007 to 2018. By adopting a double-difference model, it explores the incentive role and internal mechanism of the new Environmental Protection Law (EPL), implemented in 2015, as an environmental regulation on the environmental protection investment of enterprises, taking the new EPL’s enactment as a quasi-natural experiment. The study revealed a noteworthy and positive impact on motivation, which remained consistent even after various robustness tests. Additionally, the impact of incentives varied depending on the level of competition within the industry, financial constraints, and ownership type of the enterprises. Investigating the mechanism, it has been discovered that the incentive effect advances the environmental investment of firms through diminishing agency costs, enriching the quality of environmental information disclosure, and facilitating government subsidies to enterprises. This study not only verifies, from the factual empirical level, that environmental regulation policies can promote corporate environmental investment but also provides important evidence to support to a certain extent that the implementation of the new EPL can promote enterprises’ environmental governance behaviors. This article reveals the microeconomic effects of the new Environmental Protection Law from the perspective of corporate behavior strategies, and the research conclusions have important reference significance for the construction of national legal systems and the deepening of green development strategies.

This paper innovatively constructed an analytical and forecasting framework to predict PM2.5 concentration levels for 16 municipal districts in Shanghai. By means of XGBoost parameters adjustment, empirical mode decomposition, and model fusion, improvements are made on XGBoost prediction accuracy and stability so that prediction deviation at extreme points can be avoided. The main findings of this paper can be summarized as follows: 1) Compared with the original model, the goodness of fit of the modified XGBoost model on the test set increased by 17 %, and the root mean square error decreased by 28 %; 2) The variation of PM2.5 concentration in Shanghai has a significant seasonal (cyclical) effect, and its fluctuation period is 3 months (a quarter). In winter, the frequency of extreme value points is significantly higher than that in other seasons; 3) In terms of spatial distribution, the PM2.5 concentration in the central city of Shanghai is higher than that in the rural areas, and the PM2.5 concentration gradually decreases from center city to the surrounding areas. The innovation and contribution of this paper can be summarized as follows: 1) EEMD algorithm verified by SSA was used to decompose the original model without reconstructing all subsequences and get the best weighing among each part of the hybrid model by using variable weight assignment; 2) The city was cut into pieces according to administrative districts in avoid of the duplicate analysis when utilizing advised Kriging interpolation; 3) IDW method was applied to verified Kriging interpolation to increase the accuracy; 4) The latitude and longitude were innovatively converted into the arc length of the corresponding spherical surface; 5) Hierarchical analysis method was used to obtain the order of importance among the PM2.5 monitoring stations, which could improve the accuracy and achieve dimension reduction.

The characteristics and mechanism of the southern South China Sea (SCS) Western Boundary Current (WBC) summer-winter transition have been investigated. The transition typically starts in early October and lasts for about two weeks. Above the thermoclines (~100 m), the transition is simultaneous with depth, while below the thermoclines the transition in deeper layer significant lags that in the shallow layers. The geostrophic balance dominates the transition of WBC. Above the thermocline, the transition is determined by the barotropic pressure gradient component. Below the thermocline, the transition is determined by the competition between the barotropic and baroclinic pressures components. When the southern SCS WBC transition above the thermocline starts, the barotropic and baroclinic pressures components offset each other below the thermocline, resulting in the lag of the geostrophic balance. With the depth increases, more time is needed for the barotropic pressures component to enhance enough to dominate a geostrophic balance, which induces the transition lag with depth. Changes in the barotropic pressure gradient component are mainly due to the variations in SCS basin scale wind stress curl, while changes in the baroclinic pressure gradient component below the thermocline are associated with the warming of the deeper water column caused by the downwelling near the continental slope and the disappearing of upwelling off Vietnam.

The biochar application has been reported to have a positive effect on crop yield and nutrient utilization. However, the effects of the joint application of biochar and nitrogen (N) on soil physical properties, fruit yield, quality, crop water productivity (WP) and partial factor productivity of nitrogen (PFPN) of water-stressed greenhouse tomato under drip fertigation remain poorly understood. In this study, a two-season experiment was conducted on greenhouse tomato in autumn 2021 and spring 2022, involving two biochar application rates (0 and 30 t ha–1 only in the first season before sowing), two N fertilization rates (175 and 250 kg N ha–1), and three irrigation levels (100%, 75%, and 50% of crop evapotranspiration). The results showed that biochar application significantly decreased soil bulk density by 7–13%, but significantly increased soil porosity by 5.5%− 10% and fruit yield by 43.2–73.8% compared with the non-biochar treatment. The biochar application significantly affected the total soluble solids (TSS), soluble sugar (SS), and vitamin C of tomato fruits. The interaction of biochar application and N fertilization increased PFPN and WP by 67.4% and 76.3% in autumn 2021, and by 38.1% and 51.8% in spring 2022, respectively. Biochar rate and irrigation level had significant effects on TSS and SS contents in both seasons, but N rate significantly affected TSS in autumn 2021 only and SS in both seasons. The interaction of biochar application, N rate and irrigation level had significant effects on fruit yield. The effects of biochar rate, N rate, and irrigation level on PFPN were significant in both growing seasons. The joint application of biochar and nitrogen significantly enhanced fruit yield, quality and water-nitrogen productivity of water-stressed greenhouse tomato. The Principal Component Analysis (PCA) revealed that PC1 accounted for 47.7% and 48%of the variation in autumn 2021 and spring 2022, while PC2 accounted for 14.6% and 15.6% in autumn 2021 and spring 2022, respectively. This study underscores the significance of biochar application in drip-fertigated greenhouse tomato cultivation and highlights its sustained positive effects in the next growing season.