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Abstract Few centers routinely report aortic arch calcification (AAC) due to the lack of an easy and effective evaluation method. The association between AAC and the clinical prognosis of patients who undergo transcatheter aortic valve replacement (TAVR) is unclear. We aimed to develop a rapid method to evaluate AAC in patients who underwent TAVR and to further assess their prognosis. We enrolled 464 consecutive patients with aortic stenosis who underwent TAVR. Patients with severe (11.2%), moderate (18.5%), mild (58.2%), and no (12.1%) AAC had an estimated 3-year all-cause mortality incidence of 39.6%, 20.8%, 13.4%, and 6.7% (log rank p

Abstract Background Circular dorsal ruffles (CDRs) are large and rounded membrane ruffles that function as precursors of macropinocytosis. We recently reported that CDRs form in Hep3B hepatocellular carcinoma (HCC) cells, but not in Huh7 and HepG2 HCC cells or LO2 cells, suggesting that an unknown molecular mechanism implicates CDRs in Hep3B malignancy through macropinocytosis uptake of excessive extracellular nutrients. In this study, we investigated the cellular role and the mechanism of CDRs in Hep3B cells by focusing on the GTPase-activating protein ARAP1. Methods ARAP1 knock-out (KO) cells were generated. Confocal microscopy and high-resolution scanning electron microscopy (SEM) were used for identification of the target proteins and structure analysis, respectively. Proteasome inhibitor MG132, mitochondrial function inhibitor CCCP, ARF1 inhibitor Golgicide A, and macropinocytosis inhibitor EIPA were used to investigate the molecular mechanism. Cell proliferation and Transwell migration/invasion assays were used to investigate the role of ARAP1 in cellular malignancy. Results ARAP1 was localized to CDRs, which had reduced size following ARAP1 KO. CDRs comprised small vertical lamellipodia, the expression pattern of which was disrupted in ARAP1 KO cells. Extracellular solute uptake, rate of cell growth, and malignant potential were attenuated in KO cells. ARAP1 was also localized to mitochondria in Hep3B cells but not in the control cell lines. Mitochondrial fission protein was increased in KO cells. CCCP treatment blocked CDRs in Hep3B cells but not in controls. Surprisingly, ARAP1 expression level in Hep3B cells was lower than in Huh7, HepG2, and LO2 cells. MG132 treatment increased the ARAP1 levels in Hep3B cells, but not in Huh7 cells, revealing that ARAP1 is actively degraded in Hep3B cells. Conclusions These results strongly suggest that the aberrant expression of ARAP1 in Hep3B cells modulates CDRs via mitochondrial function, thereby resulting in excess uptake of nutrients as an initial event in cancer development. Based on these findings, we propose that the molecular mechanisms underlying the formation of CDRs, focusing on ARAP1, may serve as an effective therapeutic target in some types of HCC and cancers.

Abstract The performance of pneumatic control valves, characterized by speed, stability, and accuracy, is critical for industrial production and energy efficiency. Traditional PID and fuzzy control methods face limitations in achieving high-precision control due to structural constraints. This study proposes a fractional-order proportional-integral-derivative (FOPID) controller optimized for pneumatic control valves, incorporating a novel overshoot-penalty objective function. To enhance optimization, the Hippopotamus Optimization (HO) is improved with Genetic Algorithm (GA). Simulation and experimental results demonstrate the proposed GAHO-based FOPID controller achieves a settling time of 5.25 s and an overshoot of 0.88%, significantly surpassing conventional methods. These results establish that the proposed FOPID controller as an effective solution for improving the stability, efficiency, and safety of pneumatic control systems in industrial applications.

Abstract Background The immune landscape associated with different subtypes of intestinal metaplasia (IM) and early gastric cancer (EGC) remains unclear. This study aimed to investigate the immune landscape of complete intestinal metaplasia (CIM), incomplete intestinal metaplasia (IIM), and EGC, as well as the underlying mechanisms of EGC progression. Methods Gastric biopsy samples were collected from five patients with CIM, six patients with IIM, and four patients with EGC, followed by single-cell RNA sequencing. Multiplex immunohistochemical staining was employed to validate the samples from the aforementioned patients. To elucidate the potential mechanisms involved, in vitro coculture experiments were conducted using FOLR2+/FOLR2− macrophages and CD8+ T cells. Flow cytometry was utilized to investigate the biological functions of FOLR2+ macrophages in the progression of EGC. Results Five subpopulations of macrophages were identified in CIM, IIM and EGC samples. FOLR2+ macrophages possess antitumor immune potential, and the proportion of FOLR2+ macrophage gradually decreased from the CIM stage to the IIM and EGC stages. FOLR2+ macrophages were significantly positively correlated with CD8+ T cells and activated the cytotoxicity of CD8+ T cells via antigen cross-presentation. Additionally, during the progression of EGC, epithelial cells progressively upregulated APP expression, thus inducing necroptosis of FOLR2+ macrophages via the APP‒TNFRSF21 axis. Conclusions Our work provides an understanding of the potential mechanisms underlying the malignant transformation of IM mediated by FOLR2+ macrophages. Graphical Abstract

Abstract Extensive evidence underscores the pivotal role of socioeconomic status (SES) in shaping cancer-related outcomes. However, synthesizing definitive and actionable insights from the expansive body of literature remains a significant challenge. To elucidate the associations between SES, cancer outcomes, and the overall cancer burden, we conducted a comprehensive burden estimation coupled with an umbrella review of relevant meta-analyses. Our findings reveal that robust or highly suggestive meta-analytic evidence supports only a limited number of these associations. Individuals with lower SES, compared to those with higher SES, are disproportionately disadvantaged by reduced access to immunotherapy, KRAS testing for colorectal cancer, targeted cancer therapies, and precision treatments for melanoma. Additionally, they exhibit lower rates of breast cancer screening and higher incidence rates of lung cancer. Furthermore, countries with a higher Human Development Index demonstrate a substantially greater burden related cancer incidence, with this disparity being more pronounced among men than women.

Abstract Background Current cardiovascular prevention strategies are based on studies that seldom include valvular heart disease (VHD). The role of modifiable lifestyle factors on VHD progression and life expectancy among the elderly with different socioeconomic statuses (SES) remains unknown. Methods This cohort study included 164,775 UK Biobank participants aged 60 years and older. Lifestyle was determined using a five-factor scoring system covering smoking status, obesity, physical activity, diet, and sleep patterns. Based on this score, participants were then classified into “poor,” “moderate,” or “ideal” lifestyle groups. SES was classified as high or low based on the Townsend Deprivation Index. The association of lifestyle with major VHD progression was evaluated using a multistate mode. The life table method was employed to determine life expectancy with VHD and without VHD. Results The UK Biobank documented 5132 incident VHD cases with a mean follow-up of 12.3 years and 1418 deaths following VHD with a mean follow-up of 6.0 years. Compared to those with a poor lifestyle, women and men followed an ideal lifestyle had lower hazard ratios for incident VHD (0.66 with 95% CI, 0.59–0.73 for women and 0.77 with 95% CI, 0.71–0.83 for men) and for post-VHD mortality (0.58 for women, 95% CI 0.46–0.74 and 0.62 for men, 95% CI 0.54–0.73). When lifestyle and SES were combined, the lower risk of incident VHD and mortality were observed among participants with an ideal lifestyle and high SES compared to participants with an unhealthy lifestyle and low SES. There was no significant interaction between lifestyle and SES in their correlation with the incidence and subsequent mortality of VHD. Among low SES populations, 60-year-old women and men with VHD who followed ideal lifestyles lived 4.2 years (95% CI, 3.8–4.7) and 5.1 years (95% CI, 4.5–5.6) longer, respectively, compared to those with poor lifestyles. In contrast, the life expectancy gain for those without VHD was 4.4 years (95% CI, 4.0–4.8) for women and 5.3 years (95% CI, 4.8–5.7) for men when adhering to an ideal lifestyle versus a poor one. Conclusions Adopting a healthier lifestyle can significantly slow down the progression from free of VHD to incident VHD and further to death and increase life expectancy for both individuals with and without VHD within diverse socioeconomic elderly populations.

Abstract Background The high prevalence of sensory impairment and functional limitations in older adults is a significant concern, yet there is limited understanding of the relationship between these two conditions. Therefore, the objective of this study was to investigate the pathways connecting sensory impairment and functional limitations by examining serial multiple mediating effects of social isolation and cognition in older adults. Methods Using the China Health and Retirement Longitudinal Study dataset, a sample of 4871 older adults was selected. The study variables included sensory impairment, functional limitations, social isolation and cognition, and other covariates. A hierarchical multiple linear regression model was used to assess the association between sensory impairment and functional limitations. Mediation analysis was conducted to explore the sequential multiple mediating effects of social isolation and cognitive function in the relationship between sensory impairment and functional limitations. Results Our findings revealed a significant and positive association between sensory impairment and functional limitations (B = 0.615, 95% CI: 0.397, 0.834). After adjusting for social isolation and cognitive function, the impact of sensory impairment on functional limitations accounted for 87.19% of the total effect. Additionally, approximately 12.81% of the significant relationship between dual sensory impairment and functional limitations was mediated by social isolation and cognitive function. A serial multiple mediating pathway (sensory impairment → social isolation → cognition → functional limitations) was identified, with a coefficient of 0.013 (95% CI: 0.006, 0.020). Conclusions Our study provides evidence for the mediating effects of social isolation and cognition in the relationship between sensory impairment and functional limitations. Given the prevalence of functional limitations among older adults with sensory impairment, it is crucial to consider social isolation and cognitive function in efforts to reduce the burden of disability care. Future validation of these findings through longitudinal studies is necessary.

Known to be discrediting and discriminatory in nature, scholars have argued that the impact of stigma against persons with lived experiences of mental illnesses (PWLEs) is far worse than living with the symptoms of the conditions itself. Particularly in Asia where mental illnesses tend to be highly moralized, where PWLEs are often conceived as displaying poor character due to Confucius ideology or religious reasons, evidence has shown that stigma against PWLEs is much stronger in Asia than in the Western contexts. Currently, there is limited insights on the origins of mental illness stigma and how stigma is constructed into moralized forms and perpetuated across society. Underpinned by social constructionism, this systematic review and meta-ethnography paper undertook a theory-driven approach to address ‘how is mental illness stigma socially constructed amongst Asians?’ Systematic search for primary qualitative research journal papers was conducted across six databases (PubMed; Embase; PsycINFO; CINAHL; Social Science Database; SCOPUS), yielding 4516 articles. 30 articles were identified for synthesis. Results revealed how historical context of governmental (colonialism; Confucius ideology; industrialization) and religious institutions and country-specific power elites and individuals shaped the constructions of cultural stigma. Cultural stigma permeates societies through culturally dependent language via word-of-mouth (facilitated by collectivism) and media into forms of public stigma, causing a lack of trust between public and PWLEs. Individuals in societies further perpetuate stigma by means of interpreting, labelling anomalies and discriminating PWLEs based on preconceived learnt cultural prejudices that are activated during social interactions, further reinforcing public stigma. Finally, while most PWLEs anticipate stigma and self-stigmatize due to internalization of cultural and public stigma, unique to this study, a small group of PWLEs was able to resist and contest stigma due to holding socially valued roles that ‘matter most’. Recommendations for destigmatization strategies are suggested in view of these findings.

Background Somatosensory and motor dysfunctions are common after stroke, both lead to limitations in activities of daily living and social participation, there is still a lack of research evidence to analyze the relationship between the two from multiple perspectives. Objective To investigate the relationship between somatosensory and motor function among overall, upper and lower extremities in different-age-group patients within one year after stroke. Methods This prospective study enrolled the poststroke patients within one year from several hospitals in Fujian Province from October 2022 to April 2023. The sensory subscale of the Fugl-Meyer assessment (FMA-S) and the sensory subitem of National Institute of Health Stroke Scale (NIHSS) were used to evaluate the patient's somatosensory function. The motor subscale of the Fugl-Meyer assessment (FMA-M), Brunnstrom assessment, Berg Balance Scale (BBS) and the motor subitem of NIHSS were used to evaluate the patient's motor function. Modified Barthel Index (MBI) was used to evaluate the patient's activities of daily living (ADL). Hospital Anxiety and Depression Scale (HADS) was used to evaluate the patient's psychosomatic function. They were divided into two groups (the elderly group/the young and middle-aged group) according to their age, we compared the differences in general information and rehabilitation assessments between the two groups. And we analyzed the correlation between somatosensory function and motor function/ADL/psycho-psychological function. Results A total of 254 patients were included, with an average age of (61.0±12.3) years and an average disease course of 30.0 (17.0, 65.5) days. There were 112 cases (44.1%) in the elderly group and 142 cases (55.9%) in the young and middle-aged group. FMA-S and FMA-M scores were positively correlated in both groups (rs values were 0.313 and 0.171, both P

Abstract Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration. Graphical Abstract

Abstract Astragali radix (AR, namded Huangqi in Chinese) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. As a widely used ethnomedicine, the biological activities of AR include immunomodulatory, anti-hyperglycemic, anti-oxidant, anti-aging, anti-inflammatory, anti-viral, anti-tumor, cardioprotective, and anti-diabetic effects, with minimum side effects. Currently, it is known that polysaccharides, saponins, and flavonoids are the indispensable components of AR. In this review, we will elaborate the research advancements of AR on ethnobotany, ethnopharmacological practices, phytochemicals, pharmacological activities, clinical uses, quality control, production developments, and toxicology. The information is expected to assist clinicians and scientists in developing useful therapeutic medicines with minimal systemic side effects.

Abstract Colorectal carcinogenesis and progression are associated with aberrant alternative splicing, yet its molecular mechanisms remain largely unexplored. Here, we find that Microrchidia family CW-type zinc finger 2 (MORC2) binds to RRM1 domain of RNA binding motif protein 39 (RBM39), and RBM39 interacts with site 1 of pre-CDK5RAP2 exon 32 via its UHM domain, resulting in a splicing switch of cyclin-dependent kinase 5 regulatory subunit associated protein 2 (CDK5RAP2) L to CDK5RAP2 S. CDK5RAP2 S promotes invasion of colorectal cancer cells in vitro and metastasis in vivo. Mechanistically, CDK5RAP2 S specifically recruits the PHD finger protein 8 to promote Slug transcription by removing repressive histone marks at the Slug promoter. Moreover, CDK5RAP2 S, but not CDK5RAP2 L, is essential for the promotion of epithelial-mesenchymal transition induced by MORC2 or RBM39. Importantly, high protein levels of MORC2, RBM39 and Slug are strongly associated with metastasis and poor clinical outcomes of colorectal cancer patients. Taken together, our findings uncover a novel mechanism by which MORC2 promotes colorectal cancer metastasis, through RBM39-mediated pre-CDK5RAP2 alternative splicing and highlight the MORC2/RBM39/CDK5RAP2 axis as a potential therapeutic target for colorectal cancer.

The genus Kadsura Kaempf. ex Juss., which belongs to the important medicine food homology family Schisandraceae, is mainly produced in East and Southeast Asia. Most of their roots, stems, leaves, and seeds contain natural bioactive compounds such as lignans and can be used as herbal medicine in Chinese ancient medical works like “Compendium of Materia Medica”. Its fruit is widely used as an antioxidant, tonic, and hepatoprotective. On the basis of literature research, about 12 species of the genus Kadsura have been reported. The most often mentioned species are K. coccinea and K. heteroclita which are widely used in rheumatoid arthritis, cardiovascular and cerebrovascular diseases, liver injury and other diseases. In addition, more than 230 lignans in genus Kadsura plants were summarized. The mechanism and effect of biological activities such as anti-oxidation, anti-bacterial and anti-cancer were studied. Finally, the development and utilization of genus Kadsura lignans in the areas of preservation, enhancement of drug absorption, potential functional food raw materials, and cosmetics have also been mentioned, indicating that lignans have the potential for a wide range of applications in the food and pharmaceutical sectors.

Indirect aggression has become a prevalent phenomenon that erodes the social media environment. Due to the expense and the difficulty in determining objectively what constitutes indirect aggression, the traditional self-reporting questionnaire is hard to be employed in the current cyber area. In this study, we present a model for predicting indirect aggression online based on pre-trained models. Building on Weibo users’ social media activities, we constructed basic, dynamic, and content features and classified indirect aggression into three subtypes: social exclusion, malicious humour, and guilt induction. We then built the prediction model by combining it with large-scale pre-trained models. The empirical evidence shows that this prediction model (ERNIE) outperforms the pre-trained models and predicts indirect aggression online much better than the models without extra pre-trained information. This study offers a practical model to predict users’ indirect aggression. Furthermore, this work contributes to a better understanding of indirect aggression behaviors and can support social media platforms’ organization and management.

Ovarian transplantation presents significant advantages for the preservation of female fertility. Nonetheless, a substantial number of follicles are apoptosis during the process of ovarian tissue transplantation as a result of ischemic conditions. This study aimed to assess whether adipose-derived mesenchymal stem cells combined with urinary bladder matrix (ADSC/UBM) confer a greater therapeutic benefit compared to ADSCs alone. To achieve this, ADSC/UBM was applied during the autotransplantation of rat ovaries. Thirty rats were divided into five sets of six: the untreated control group (Normal), the oophorectomy group, the autograft group, the autograft + ADSCs group (ADSC), and the autograft + ADSC/UBM group (ADSC/UBM). After transplantation, the number of follicles in the ADSC/UBM group was significantly higher than that in the autograft group. Angiogenesis was enhanced following ADSC/UBM transplantation. Follicle-stimulating hormone (FSH) levels were significantly lower, and Anti-Müllerian hormone (AMH) levels were significantly higher in rats in the ADSC/UBM group than in the Autograft group. The apoptosis rate in the ADSC/UBM group decreased. The estrous cycle in the ADSC/UBM group recovered more quickly than the ADSC group. The data indicate that UBM improves ADSC retention in graft ovaries and aids in permanently restoring ovarian function, making ADSC/UBM a promising option for ovarian transplantation.

Abstract Background Cervical cancer is a human papillomavirus (HPV)-related disease. HPV type 16 (HPV16), which is the predominant cause of cervical cancer, can encode miRNAs (HPV16-miRNAs). However, the role of HPV16-miRNAs in the pathogenesis of cervical cancer remains unclear. Methods Human cervical cancer cell lines SiHa (HPV16-positive) and C33A (HPV-negative), and cervical cancer tissues were collected to investigate the expression levels of two HPV16-miRNAs (HPV16-miR-H1 and HPV16-miR-H6). The overexpression and knockdown of HPV16-miR-H1 and HPV16-miR-H6 were performed using the lentiviral vector system and miRNA inhibitors, respectively. RNA-sequencing (RNA-seq) analysis and H3K27ac chromatin immunoprecipitation and sequencing (CHIP-seq) experiments were utilized to explore the roles of HPV16-miR-H1 and HPV16-miR-H6 facilitated by enhancers. CCK8, EdU, transwell, and wound healing assays were performed to verify the effects of HPV16-miR-H1 and HPV16-miR-H6 on cell proliferation and migration. Results HPV16-miR-H1 and HPV16-miR-H6 were highly expressed in both SiHa cells and tissue samples from HPV16-positive cervical cancer patients. RNA-seq analysis showed that HPV16-miR-H1 and HPV16-miR-H6 induced the upregulation of numerous tumor progression-associated genes. H3K27ac CHIP-seq experiments further revealed that HPV16-miR-H1 and HPV16-miR-H6 modulated the expression of critical genes by regulating their enhancer activity. The functional study demonstrated that HPV16-miR-H1 and HPV16-miR-H6 increased the migratory capacity of SiHa cells. Conclusions Our data shed light on the role of HPV16-encoded miRNAs in cervical cancer, particularly emphasizing their involvement in the miRNA-enhancer-target gene system. This novel regulatory mechanism of HPV16-miRNAs provides new insights and approaches for the development of therapeutic strategies by targeting HPV16-positive cervical cancer.

Abstract Objective To observe prosthetic-associated subclinical thrombotic events (PASTE) after transcatheter aortic valve implantation (TAVI) by cardiac CTA, and assess their impact on long-term patient outcomes. Materials We prospectively and consecutively enrolled 188 patients with severe aortic stenosis treated with TAVI from February 2014 to April 2017. At 5 years, 61 of 141 survived patients who had completed annual follow-up CTA (≥ 5 years) were included. We analyzed PASTE by CTA, including hypoattenuated leaflet thickening (HALT), sinus filling defect (SFD), and prosthesis filling defect (PFD). The primary outcome was a major adverse cardiovascular composite outcome (MACCO) of stroke, cardiac re-hospitalization, and bioprosthetic valve dysfunction (BVD); the secondary outcomes were bioprosthetic hemodynamics deterioration (PGmean) and cardiac dysfunction (LVEF). Results During a median follow-up time of 5.25 years, long-term incidence of HALT, SFD, and PFD were 54.1%, 37.7%, and 73.8%, respectively. In the primary outcome, SFD and early SFD were associated with the MACCO (SFD: p = 0.005; early SFD: p = 0.018), and SFD was a predictor of MACCO (HR: 2.870; 95% CI: 1.010 to 8.154, p = 0.048). In the secondary outcomes, HALT was associated with increased PGmean (p = 0.031), while persistent HALT was correlated with ΔPGmean (β = 0.38, p = 0.035). SFD was negatively correlated with ΔLVEF (β = −0.39, p = 0.041), and early SFD was negatively correlated with LVEF and ΔLVEF (LVEF: r = −0.50, p = 0.041; ΔLVEF: r = −0.53, p = 0.030). Conclusions PASTE were associated with adverse long-term outcomes, bioprosthetic hemodynamics deterioration, and cardiac dysfunction. In particular, SFD was a predictor of MACCO and may be a potential target for anticoagulation after TAVI (NCT02803294). Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02803294. Critical relevance statement PASTE, especially SFD, after TAVI based on cardiac CTA findings impacts the long-term outcomes of patients which is a predictor of long-term major adverse outcomes in patients and may be a potential target for anticoagulation after TAVI. Key Points Transcatheter aortic valve implantation is being used more often; associated subclinical thromboses have not been thoroughly evaluated. Prosthetic-associated subclinical thrombotic events were associated with adverse outcomes, bioprosthetic hemodynamics deterioration, and cardiac dysfunction. Studies should be directed at these topics to determine if they should be intervened upon. Graphical Abstract

Objective To summarize the clinical features, serological features, blood transfusion protocols and treatment of 3 cases of passenger lymphocyte syndrome(PLS) after ABO-incompatibility liver and renal transplantation in our hospital, in order to provide guidance for comprehensive clinical understanding and recognition of this disease, especially early recognition and treatment. Methods By collecting the basic information of the patients and the time of cross-matching incompatibility of homologous blood after transplantation, observing the skin yellow staining, detecting hemoglobin value and other hemolysis indexes, and blood group serological detection results before and after transfusion, the diagnosis and analysis were performed. The diagnosis and treatment effect of PLS were analyzed by collecting the clinical outcome information after immunization and blood transfusion. Results Three cases of ABO-incompatible liver transplantation showed decreased hemoglobin and hemolysis, incompatible cross-matching of homologous blood, and anti-A and anti-B IgG antibodies were confirmed by serological test. After treatment such as immunosuppression and plasma exchange, blood transfusion was effective, hemolysis was improved, and antibodies gradually disappeared. Conclusion ABO blood group antibody screening, unexpected antibody screening and direct antiglobulin test(DAT)should be performed regularly for ABO-incompatible liver and renal transplantation cases, in order to detect the PLS early. A series of laboratory tests related to PLS should be performed in time to diagnose and adjust the treatment plan, including transfusion strategy, when homologous cross-matching is incompatible.

Abstract Organic solar cells (OSCs) are considered as a crucial energy source for flexible and wearable electronics. Pseudo-planar heterojunction (PPHJ) OSCs simplify the solution preparation and morphology control. However, non-halogenated solvent-printed PPHJ often have an undesirable vertical component distribution and insufficient donor/acceptor interfaces. Additionally, the inherent brittleness of non-fullerene small molecule acceptors (NFSMAs) in PPHJ leads to poor flexibility, and the NFSMAs solution shows inadequate viscosity during the printing of acceptor layer. Herein, we propose a novel approach termed polymer-incorporated pseudo-planar heterojunction (PiPPHJ), wherein a small amount of polymer donor is introduced into the NFSMAs layer. Our findings demonstrate that the incorporation of polymer increases the viscosity of acceptor solution, thereby improving the blade-coating processability and overall film quality. Simultaneously, this strategy effectively modulates the vertical component distribution, resulting in more donor/acceptor interfaces and an improved power conversion efficiency of 17.26%. Furthermore, PiPPHJ-based films exhibit superior tensile properties, with a crack onset strain of 12.0%, surpassing PPHJ-based films (9.6%). Consequently, large-area (1 cm2) flexible devices achieve a considerable efficiency of 13.30% and maintain excellent mechanical flexibility with 82% of the initial efficiency after 1000 bending cycles. These findings underscore the significant potential of PiPPHJ-based OSCs in flexible and wearable electronics.

China is the world’s largest agricultural country and is also deeply affected by extreme weather. Water infrastructure is a crucial solution to improve the climate adaptability of the agricultural industry. This study aimed to explore the above adaptive processes of the agricultural industry from a resilience perspective. This study builds a multi-level system dynamics (SD) model to assess the development of the agricultural industry and water infrastructure, predict the future resilience development trend, identify the key influencing factors, and simulate the effectiveness of different water infrastructure measures. The results show that (1) water infrastructure involving various climate adaptation measures significantly promotes the development of the agricultural industry. (2) Agricultural output, water infrastructure investment, and other fixed asset investments strongly improve the resilience, and the impact of the crop planting area is limited. (3) The resilience level is higher under the eco-friendly water conservation scenario than in the water supply security scenario and flood disaster prevention scenario. Such information will promote the sustainable development of the agricultural industry and future climate adaptation policy-making.

Infertility is a growing health concern among many couples worldwide. Men account for half of infertility cases. CatSper, a sperm-specific Ca2+ channel, is expressed on the cell membrane of mammalian sperm. CatSper plays an important role in male fertility because it facilitates the entry of Ca2+ necessary for the rapid change in sperm motility, thereby allowing it to navigate the hurdles of the female reproductive tract and successfully locate the egg. Many pollutants present in the environment have been shown to affect the functions of CatSper and sperm, which is a matter of capital importance to understanding and solving male infertility issues. Environmental pollutants can act as partial agonists or inhibitors of CatSper or exhibit a synergistic effect. In this article, we briefly describe the structure, functions, and regulatory mechanisms of CatSper, and discuss the body of literature covering the effects of environmental pollutants on CatSper.

Abstract Cellular senescence is a significant contributor to intervertebral disc aging and degeneration. However, the application of senotherapies, such as senomorphics targeting senescence markers and the senescence‐associated secretory phenotype (SASP), remains limited due to challenges in precise delivery. Given that the natural killer group 2D (NKG2D) ligands are increased on the surface of senescent nucleus pulposus (NP) cells, the NKG2D‐overexpressing NP cell membranes (NNPm) are constructed, which is expected to achieve a dual targeting effect toward senescent NP cells based on homologous membrane fusion and the NKG2D‐mediated immunosurveillance mechanism. Then, mesoporous silica nanoparticles carrying a peroxisome proliferator‐activated receptor‐ɣ coactivator 1α (PGC1α)inducer (SP) are coated with NNPm (SP@NNPm) and it is found that SP@NNPm selectively targets senescent NP cells, and the SP cores exhibit pH‐responsive drug release. Moreover, SP@NNPm effectively induces PGC1α‐mediated mitochondrial biogenesis and mitigates senescence‐associated markers induced by oxidative stress and the SASP, thereby alleviating puncture‐induced senescence and disc degeneration. This dual‐targeting nanotherapeutic system represents a novel approach to delivery senomorphics for disc degeneration treatment.

RationaleSepsis is a life-threatening organ dysfunction and lack of effective measures in the current. Exosomes from mesenchymal stem cells (MSCs) reported to alleviate inflammation during sepsis, and the preconditioning of MSCs could enhance their paracrine potential. Therefore, this study investigated whether exosomes secreted by lipopolysaccharide (LPS)-pretreated MSCs exert superior antiseptic effects, and explored the underlying molecular mechanisms.MethodsExosomes were isolated and characterized from the supernatants of MSCs. The therapeutic efficacy of normal exosomes (Exo) and LPS-pretreated exosomes (LPS-Exo) were evaluated in terms of survival rates, inflammatory response, and organ damage in an LPS-induced sepsis model. Macrophages were stimulated with LPS and treated with Exo or LPS-Exo to confirm the results of the in vivo studies, and to explain the potential mechanisms.ResultsLPS-Exo were shown to inhibit aberrant pro-inflammatory cytokines, prevent organ damages, and improve survival rates of the septic mice to a greater extent than Exo. In vitro, LPS-Exo significantly promoted the M2 polarization of macrophages exposed to inflammation. miRNA sequencing and qRT-PCR analysis identified the remarkable expression of miR-150–5p in LPS-Exo compared to that in Exo, and exosomal miR-150–5p was transferred into recipient macrophages and mediated macrophage polarization. Further investigation demonstrated that miR-150–5p targets Irs1 in recipient macrophages and subsequently modulates macrophage plasticity by down-regulating the PI3K/Akt/mTOR pathway.ConclusionThe current findings highly suggest that exosomes derived from LPS pre-conditioned MSCs represent a promising cell-free therapeutic method and highlight miR-150–5p as a novel molecular target for regulating immune hyperactivation during sepsis.

Abstract The Holocene temperature conundrum, the discrepancy between proxy-based Holocene global cooling and simulated global annual warming trends, remains controversial. Meanwhile, reconstructions and simulations show inconsistent spatial patterns of terrestrial temperature changes. Here we report Holocene alkenone records to address spatial patterns over mid-latitude Eurasia. In contrast with long-term cooling trends in warm season temperatures in northeastern China, records from southwestern Siberia are characterized by colder conditions before ~6,000 years ago, thus long-term warming trends. Together with existing records from surrounding regions, we infer that colder airmass might have prevailed in the interior of mid-latitude Eurasian continent during the early to mid-Holocene, perhaps associated with atmospheric response to remnant ice sheets. Our results challenge the proposed seasonality bias in proxies and modeled spatial patterns in study region, highlighting that spatial patterns of Holocene temperature changes should be re-considered in record integrations and model simulations, with important implications for terrestrial hydroclimate changes.

Abstract HOOK3, a member of the human hook microtubule-tethering protein family, has been implicated in the progression of cancer. However, the role of HOOK3 in the pathogenesis of gastric cancer (GC) remains incompletely understood. In this study, we investigated the expression of HOOK3 protein in GC tissues using immunohistochemistry (IHC). The findings of our study indicate that the expression levels of HOOK3 in GC tissues were relatively low. Furthermore, a significant negative association was seen between HOOK3 expression and the prognosis of patients with GC. The suppression of HOOK3 resulted in a notable increase in the proliferation, migration, invasion, and survival of GC cells. Conversely, the overexpression of HOOK3 had the opposite impact, reducing these cellular processes. Moreover, in vivo tests have shown evidence that the overexpression of HOOK3 significantly inhibited the formation of tumors and the spread of GC cells to the lungs. In a mechanistic manner, the analysis of RNA-seq data demonstrated that the knockdown of HOOK3 resulted in a notable increase in the expression of vascular endothelial growth factor A (VEGFA) in GC cells. Furthermore, the upregulation of VEGFA counteracted the impacts of HOOK3 upregulation on the proliferation, migration, invasion, and survival of GC cells. Furthermore, it was revealed that specificity protein 1 (SP1) exhibited the ability to bind to the promoter region of VEGFA. Moreover, the overexpression of SP1 successfully counteracted the inhibitory impact of HOOK3 overexpression on the expression of VEGFA in GC cells. In summary, the results of our study indicate that HOOK3 has a role in inhibiting the growth, migration, invasion, and survival of GC cells by modulating the SP1/VEGFA pathway. These findings contribute significant knowledge to our understanding of the underlying mechanisms involved in the development of GC.

Abstract Background In China, individuals diagnosed with esophageal cancer are confronted with an elevated risk of nutritional inadequacy or malnutrition throughout the course of their disease, a condition that contributes to various adverse clinical outcomes. A vast corpus of data are burgeoning at an unprecedented rate, primarily due to the revolutionary growth of digitalization technologies and artificial intelligence, notably within the domains of health care and medicine. The purpose of this investigation is to initiate the development of a nutritional screening and assessment indicator framework for patients with esophageal cancer within the Chinese context. We seek to furnish an instrumental reference to facilitate preparations for the forthcoming era of advanced, “deep,” evidence‐based medicine. Methods An integrative methodology was employed to forge the preliminary draft of the nutritional screening and assessment indicator system for preoperative patients with esophageal cancer. This encompassed a rigorous literature survey, in‐depth clinical practice investigation, and the facilitation of expert panel discussions. Thereafter, two iterative consultation phases were conducted using the Delphi method in China. The analytic hierarchy process was deployed to ascertain the weighting of each index within the definitive evaluation indicator system. Results The effective response rates for the dual rounds of expert consultation were 91.7% and 86.4%, with commensurate authority coefficients of 0.97 and 0.91. The Kendall harmony coefficients were ascertained to be 0.19 and 0.14 (p

Cordyceps primarily consists of ascomycetes, a parasitic fungus that infects insects and arthropods. Recently, Cordyceps has been shown to manifest a diverse range of pharmacological activities, rendering it applicable for the treatment and mitigation of various diseases, such as diabetes, acute liver injury, and colitis. Many active constituents have been identified from Cordyceps sinensis, including cordycepin, adenosine, sterols, and polysaccharides. Polysaccharides constitute a primary active component of Cordyceps, exhibiting immunomodulatory effects. We searched the Web of Science database with the keywords of cordyceps, polysaccharide, and immune modulation; collected related studies from 2004 to 2024; and eliminated articles with low influence and workload. A review of the research advancements regarding the immunomodulatory effects of Cordyceps polysaccharides was conducted with the aim of furnishing valuable reference information. Research indicates that polysaccharides exhibiting immunomodulatory activity are predominantly sourced from Cordyceps sinensis and Cordyceps militaris. Immunological experimental results demonstrate that Cordyceps polysaccharides can augment the activities of macrophages, lymphocytes, and dendritic cells while fostering the expression of immune-active substances such as cytokines and chemokines. Furthermore, animal experiments have substantiated the immunomodulatory effects of Cordyceps polysaccharides. These effects encompass ameliorating immune suppression induced by drugs or radiation, enhancing immune organ indices, elevating the expression of immunoreactive substances, and mitigating immune evasion prompted by tumors. In conclusion, Cordyceps polysaccharides exhibit significant immunomodulatory activity and merit further investigation.

Traffic prediction is crucial for transportation management and user convenience. With the rapid development of deep learning techniques, numerous models have emerged for traffic prediction. Recurrent Neural Networks (RNNs) are extensively utilized as representative predictive models in this domain. This paper comprehensively reviews RNN applications in traffic prediction, focusing on their significance and challenges. The review begins by discussing the evolution of traffic prediction methods and summarizing state-of-the-art techniques. It then delves into the unique characteristics of traffic data, outlines common forms of input representations in traffic prediction, and generalizes an abstract description of traffic prediction problems. Then, the paper systematically categorizes models based on RNN structures designed for traffic prediction. Moreover, it provides a comprehensive overview of seven sub-categories of applications of deep learning models based on RNN in traffic prediction. Finally, the review compares RNNs with other state-of-the-art methods and highlights the challenges RNNs face in traffic prediction. This review is expected to offer significant reference value for comprehensively understanding the various applications of RNNs and common state-of-the-art models in traffic prediction. By discussing the strengths and weaknesses of these models and proposing strategies to address the challenges faced by RNNs, it aims to provide scholars with insights for designing better traffic prediction models.

Abstract Network pharmacology can ascertain the therapeutic mechanism of drugs for treating diseases at the level of biological targets and pathways. The effective mechanism study of traditional Chinese medicine (TCM) characterized by multi-component, multi-targeted, and integrative efficacy, perfectly corresponds to the application of network pharmacology. Currently, network pharmacology has been widely utilized to clarify the mechanism of the physiological activity of TCM. In this review, we comprehensively summarize the application of network pharmacology in TCM to reveal its potential of verifying the phenotype and underlying causes of diseases, realizing the personalized and accurate application of TCM. We searched the literature using “TCM network pharmacology” and “network pharmacology” as keywords from Web of Science, PubMed, Google Scholar, as well as Chinese National Knowledge Infrastructure in the last decade. The origins, development, and application of network pharmacology are closely correlated with the study of TCM which has been applied in China for thousands of years. Network pharmacology and TCM have the same core idea and promote each other. A well-defined research strategy for network pharmacology has been utilized in several aspects of TCM research, including the elucidation of the biological basis of diseases and syndromes, the prediction of TCM targets, the screening of TCM active compounds, and the decipherment of mechanisms of TCM in treating diseases. However, several factors limit its application, such as the selection of databases and algorithms, the unstable quality of the research results, and the lack of standardization. This review aims to provide references and ideas for the research of TCM and to encourage the personalized and precise use of Chinese medicine.

ABSTRACT: Hypocalcemia in dairy cows is associated with a decrease of neutrophil adhesion and phagocytosis, an effect driven partly by changes in the expression of store-operated Ca2+ entry (SOCE)-related molecules. It is well established in nonruminants that neutrophils obtain the energy required for immune function through glycolysis. Whether glycolysis plays a role in the acquisition of energy by neutrophils during hypocalcemia in dairy cows is unknown. To address this relationship, we performed a cohort study and then a clinical trial. Neutrophils were isolated at 2 d postcalving from lactating Holstein dairy cows (average 2.83 ± 0.42 lactations, n = 6) diagnosed as clinically healthy (CON) or with plasma concentrations of Ca2+

Abstract Background This study aimed to construct a risk prediction model to estimate the odds of osteoporosis (OP) in elderly patients with type 2 diabetes mellitus (T2DM) and evaluate its prediction efficiency. Methods This study included 21,070 elderly patients with T2DM who were hospitalized at six tertiary hospitals in Southwest China between 2012 and 2022. Univariate logistic regression analysis was used to screen for potential influencing factors of OP and least absolute shrinkage. Further, selection operator regression (LASSO) and multivariate logistic regression analyses were performed to select variables for developing a novel predictive model. The area under the receiver operating characteristic curve (AUROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to evaluate the performance and clinical utility of the model. Results The incidence of OP in elderly patients with T2DM was 7.01% (1,476/21,070). Age, sex, hypertension, coronary heart disease, cerebral infarction, hyperlipidemia, and surgical history were the influencing factors. The seven-variable model displayed an AUROC of 0.713 (95% confidence interval [CI]:0.697–0.730) in the training set, 0.716 (95% CI: 0.691–0.740) in the internal validation set, and 0.694 (95% CI: 0.653–0.735) in the external validation set. The optimal decision probability cut-off value was 0.075. The calibration curve (bootstrap = 1,000) showed good calibration. In addition, the DCA and CIC demonstrated good clinical practicality. An operating interface on a webpage ( https://juntaotan.shinyapps.io/osteoporosis/ ) was developed to provide convenient access for users. Conclusions This study constructed a highly accurate model to predict OP in elderly patients with T2DM. This model incorporates demographic characteristics and clinical risk factors and may be easily used to facilitate individualized prediction.

The intervertebral disc is not isolated from other tissues. Recently, abundant research has linked intervertebral disc homeostasis and degeneration to various systemic diseases, including obesity, metabolic syndrome, and diabetes. Organokines are a group of diverse factors named for the tissue of origin, including adipokines, osteokines, myokines, cardiokines, gastrointestinal hormones, and hepatokines. Through endocrine, paracrine, and autocrine mechanisms, organokines modulate energy homeostasis, oxidative stress, and metabolic balance in various tissues to mediate cross-organ communication. These molecules are involved in the regulation of cellular behavior, inflammation, and matrix metabolism under physiological and pathological conditions. In this review, we aimed to summarize the impact of organokines on disc homeostasis and degeneration and the underlying signaling mechanism. We focused on the regulatory mechanisms of organokines to provide a basis for the development of early diagnostic and therapeutic strategies for disc degeneration.

Hakka rice wine is produced from grains by co-fermentation with abundant microbes in an open fermentation environment. Indigenous microbiota and enzymes convert the nutrients in grains into flavor compounds through enzymatic biochemical reactions and microbial metabolism. High-throughput sequencing technology revealed that non-Saccharomyces yeasts dominated the traditional fermentation process, with genera such as Kodamaea ohmeri, Candida orthopsilosis, and Trichosporon asteroides forming a dynamic community that highly correlated with the evolution of 80 volatile compounds in Hakka rice wine. Among the 104 volatile compounds detected by GC–MS, 22 aroma-active compounds with relative odor activity values (ROAV) > 1 were quantified, 11 of which made significant contributions (P