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RNA plays an extensive role in a multi-dimensional regulatory system, and its biomedical relationships are scattered across numerous biological studies. However, text mining works dedicated to the extraction of RNA biomedical relations remain limited. In this study, we established a comprehensive and reliable corpus of RNA biomedical relations, recruiting over 30,000 sentences manually curated from more than 15,000 biomedical literature. We also updated RIscoper 2.0, a BERT-based deep learning tool to extract RNA biomedical relation sentences from literature. Benefiting from approximately 100,000 annotated named entities, we integrated the text classification and named entity recognition tasks in this tool. Additionally, RIscoper 2.0 outperformed the original tool in both tasks and can discover new RNA biomedical relations. Additionally, we provided a user-friendly online search tool that enables rapid scanning of RNA biomedical relationships using local and online resources. Both the online tools and data resources of RIscoper 2.0 are available at http://www.rnainter.org/riscoper.

Abstract Background Public health nutrition recommendations and clinical dietary interventions emphasize eating healthy food at home, implicitly requiring household foodwork. Household foodwork is defined as the physical and mental tasks a household does for eating meals and snacks. Because no tools exist to measure it, how much time people spend doing household foodwork and the foodwork barriers they experience remain unknown. The objective of the present research was to develop the first stand-alone household foodwork assessment tool. Methods Through informal interviews with partners with lived experience, clinicians, and researchers, a literature review, a stakeholder meeting of advisors, and a two-round electronic Delphi process including face/content validation by expert panelists (n = 21), we developed the 10-question household foodwork interactional assessment questionnaire (FIA-Q10). An optional accompanying module was developed to collect self-identified demographic data to provide context for understanding how social-structural positionality factors may interact to influence foodwork. Results The FIA-Q10 assesses the domains of household composition, frequency of eating at home, special diets within a household, foodwork stress intensity, foodwork barriers, desired supports related to foodwork, and time use for foodwork. The FIA-Q10 measures time use for four subdomains of foodwork among individuals and their households: (1) planning, (2) getting, (3) preparing/cooking, and (4) cleaning up food. In the second Delphi round, the FIA-Q10 scored 95% for language appropriateness, 67% for visual appropriateness, 95% for relevance, 95% for representativeness, and 95% for distribution. Suggested improvements were implemented. All Delphi panelists (100%) reported they would consider using the FIA-Q10. Conclusions The FIA-Q10’s development is the first step towards a standardized assessment of foodwork, enabling examination of challenges in foodwork that may impact nutrition and nutrition equity. Future research will focus on FIA-Q10 validation in multiple populations.

Abstract Background Hepatitis B virus-related acute-on-chronic liver failure (HBV–ACLF) is frequently accompanied by short-term morbidity and mortality. However, there have been no studies on the associations between baseline clinicopathologic characteristics at hospital admission and clinical prognosis after receiving artificial liver therapy. Therefore, the current study aimed to develop a prognostic nomogram for predicting the outcomes of patients with HBV–ACLF following artificial liver support. Methods A retrospective study of 110 consecutive patients who were diagnosed with HBV–ACLF between January 2018 and August 2022 was conducted. First, univariate and multivariate logistic regression analyses were performed to determine the independent prognostic factors significantly associated with patient outcomes. Moreover, a predictive nomogram model underlying the prognostic factors was established and further evaluated. The area under the curve (AUC) was used to gauge the predictive accuracy. The calibration curve and decision curve analysis (DCA) were employed to assess the discriminability and clinical effectiveness, respectively. Results In patients with HBV–ACLF, multivariate logistic analysis revealed that age ≥ 40 years (OR 6.76, p = 0.025), middle-stage liver failure (OR 49.96, p

Abstract Adequate nutrition in a hospital setting is essential for achieving optimal health outcomes in oncology patients. This study specifically investigated the interrelationships between nutritional status, daily habits, and hospital length of stay (LOS) in ovarian cancer patients undergoing chemotherapy. A prospective longitudinal study was conducted from August 2019 to January 2022 in a tertiary hospital. Throughout the study, nutritional status, biochemical indicators, diet, and physical activity were meticulously recorded at different stages of chemotherapy: before chemotherapy (T0), the first course (T1), third course (T2), and fifth course (T3). To determine the factors influencing LOS, a generalized estimation equation (GEE) was employed. A total of 460 patients completed the follow-up period. The findings revealed a decline in nutritional risk among patients by 9.90% at T1, 17.62% at T2 and 18.26% at T3 (χ 2 = 79.220, P

Abstract Cinnamomum cassia Presl. is a subtropical plant that is used for food and medicine. Climate change has changed the suitable habitats of medicinal plants, which might have repercussions for the efficacy of herbal remedies. In this study, the potential distribution in each period of Cinnamomum cassia was predicted and the quality in different suitable habitats was evaluated. According to the results, (1) precipitation, temperature, and soil are the primary environmental variables influencing C. cassia distribution. (2) The high-suitable habitats of current climate scenarios were predominantly located in the southern regions (Guangdong and Guangxi etc.) of China, with an area of 706,129.08 km2. Under future climate scenarios, suitable habitats will increasingly move northward, with a greater concentration south of the Yangtze River, particularly in the 2090s SSP585 scenario, the total area of newly extended suitable habitat reaches 312,963.53 km2. (3) HPLC and FTIR, combined with chemometrics, can be effective methods for identifying different suitable habitats of C. cassia. The content of trans-cinnamaldehyde (0.85%) is significantly higher in the high suitability habitat compared to the medium-low suitability habitat (0.30%). Our findings can offer valuable guidance for the identification of suitable C. cassia cultivation areas in China, as well as for the evaluation of C. cassia resource quality and the rational use of resources in different suitable habitats.

Abstract Cancer cells encounter unavoidable stress during tumor growth. The stress-induced transcription factor, activating transcription factor 4 (ATF4), has been reported to upregulate various adaptive genes involved in salvage pathways to alleviate stress and promote tumor progression. However, this effect is unknown in clear cell renal cell carcinoma (ccRCC). In this study, we found that ATF4 expression was remarkably upregulated in tumor tissues and associated with poor ccRCC outcomes. ATF4 depletion significantly impaired ccRCC cell proliferation, migration, and invasion in vitro and in vivo by inhibiting the AKT/mTOR and epithelial–mesenchymal transition (EMT)-related signaling pathway. RNA sequencing and functional studies identified nuclear protein 1 (NUPR1) as a key downstream target of ATF4 for repressing ferroptosis and promoting ccRCC cell survival. In addition, targeting ATF4 or pharmacological inhibition using NUPR1 inhibitor ZZW115 promoted antitumor immunity in syngeneic graft mouse models, represented by increased infiltration of CD4+ and CD8+ T cells. Furthermore, ZZW115 could improve the response to the PD-1 immune checkpoint blockade. The results demonstrate that the ATF4/NUPR1 signaling axis promotes ccRCC survival and facilitates tumor-mediated immunosuppression, providing a set of potential targets and prognostic indicators for ccRCC patients. Graphical abstract

Abstract Bacteria-derived H2S plays multifunctional protective roles against antibiotics insult, and the H2S biogenesis pathway is emerging as a viable target for the antibacterial adjuvant design. However, the development of a pan-inhibitor against H2S-synthesizing enzymes is challenging and underdeveloped. Herein, we propose an alternative strategy to downregulate the H2S levels in H2S-producing bacteria, which depletes the bacteria-derived H2S chemically by H2S scavengers without acting on the synthesizing enzymes. After the screening of chemically diversified scaffolds and a structural optimization campaign, a potent and specific H2S scavenger is successfully identified, which displays efficient H2S depletion in several H2S-producing bacteria, potentiates both bactericidal agents and photodynamic therapy, enhances the bacterial clearance of macrophages and polymorphonuclear neutrophils, disrupts the formation of bacterial biofilm and increases the sensitivity of bacterial persister cells to antibiotics. Most importantly, such an H2S scavenger exhibits sensitizing effects with gentamicin in Pseudomonas aeruginosa -infected pneumonia and skin wound female mouse models. In aggregate, our results not only provide an effective strategy to deplete bacteria-derived H2S and establish the H2S biogenesis pathway as a viable target for persisters and drug-resistant bacteria, but also deliver a promising antibacterial adjuvant for potential clinical translation.

Abstract Background The association between plasma free fatty acid (FFA) and the outcomes in the heart failure (HF) patients remains unclear. Methods A cohort study among HF patients was performed. Plasma FFA was analyzed as both a continuous and a categorical variable (grouped by tertiles) to assess its association with composite cardiovascular (CV) death and HF hospitalization (CV death & HHP), CV death alone, and all-cause mortality (ACM) using Cox regression models. Subgroup analyses of HF patients with preserved ejection fraction (HFpEF) and mildly reduced/reduced ejection fraction (HFmrEF/HFrEF) were performed. This work also assessed the effectiveness of combining FFA and NT-pro BNP biomarkers for risk stratification by calculating the concordance index (C-index). Results Among the 4,109 HF patients, FFA levels exceeding 0.4–0.42 mmol/L were associated with increased risks of the three outcomes. Patients in the highest FFA tertile faced greater risks than those in the lowest tertile. Adjusted hazard ratios were 1.32 (95% CI: 1.11–1.58) for CV death & HHP, 1.45 (95% CI: 1.16–1.82) for CV death, and 1.39 (95% CI: 1.15–1.68) for ACM, with a maximum follow-up of 8 years (median: 25 months). Subgroup analyses revealed that elevated FFA levels consistently predicted worse outcomes in both HFmrEF/HFrEF and HFpEF patients. The C-index for predicting outcomes was significantly greater when NT-pro BNP and FFA were combined than when NT-pro BNP was used alone (P

Abstract The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is a valuable and easy-to-use method for assessing acute ischemic stroke. It aids in identifying suitable candidates for thrombolytic therapies and evaluating treatment effectiveness. However, ASPECTS evaluation primarily relies on visual observation in current clinical practice, lacking a common standardized space. Additionally, different doctors may have varying clinical experiences, leading to a poor inter-reader agreement and potential errors in the final ASPECTS scoring. To address these issues and fill in the absence of a publicly available ASPECTS atlas, this work constructs age-specific Chinese ASPECTS atlases based on non-contrast computed tomography images of 281 healthy subjects across different age groups. Images of different age groups are warped into respective common averaged spaces, where the average intensity atlases are computed. More importantly, 10 ASPECTS regions can be obtained during this process. We develop an automated ASPECTS region mapping pipeline and collect an independent dataset to validate our atlas. The results prove that the age-specific ASPECTS atlas is of great promise in clinical availability.

Abstract This study aimed to identify predictive factors for the prognosis of acute-on-chronic liver disease (AoCLD) due to both hepatitis B virus (HBV) and alcohol and to develop prognostic models to improve treatment management. AoCLD patients with HBV and alcohol as etiological factors were selected from two multicenter prospective cohorts (NCT02457637,NCT03641872) and included in separate training and validation cohorts (n = 180 and n = 148). In the training cohort, the CATCH-LIFE A nomogram (based on age, bilirubin, international normalized ratio, serum sodium, and hepatic encephalopathy score) and CATCH-LIFE B nomogram (based on age, bilirubin, international normalized ratio, serum albumin, white blood cell, platelet count, and hepatic encephalopathy score) had discriminatory ability for predicting 28-day (c-indexes of 0.910 and 0.899) and 90-day mortality (c-indexes of 0.878 and 0.887, respectively). The area under the curve values for 28-day and 90-day mortality prediction by the CATCH-LIFE A nomogram were 0.922 (95% CI : 0.874, 0.971) and 0.905 (0.856, 0.956), respectively, while those for the CATCH-LIFE B nomogram were 0.916(0.861,0.972) and 0.915 (0.866,0.964), respectively. Similar performance results were observed in the validation cohort. Optimal cut-off scores for each nomogram could be used for patient stratification in high- and low-risk groups, and the high-risk groups showed shorter survival times than the low-risk groups in both the training and validation cohorts. Two nomograms constructed from the first short-term follow-up data from patients with AoCLD due to combined HBV infection and alcohol exposure showed good predictive performance for 28-day and 90-day mortality and might be used to guide clinical management.

Abstract Background The post COVID-19 health condition of Chinese residents infected with Omicron is not clear after the change of epidemic prevention policies. This study aimed to clarify the epidemiology and associated factors about health status of rehabilitation patients. Methods A quick questionnaire study based on C19-YRSm was conducted in mainland China through internet from May 1, 2023, to May 7, 2023. Chinese native speakers infected with Omicron variant agreed to participate were included. Persisting symptom and living habits were simultaneously inquired. Logistic regression analysis was used to identify the associated factors. Results In this study 753 individuals were included. Of whom 57.90% were males, 89.38% did not seek medical service, 99.47% recovered within less than 120 days. Breathlessness (47.68%), cognitive impairment (44.89%), Anxiety/mood changes (33.20%), pain/discomfort (32.94%), fatigue or tiredness not improved by rest (32.27%) and post-exertional malaise (30.01%) were the top reported key symptoms. Less than 10% respondents reported functional limitations. The prevalence of fever was reported greater than that of other symptoms, with dry eyes at 14.87%, appetite change at 14.34%, and hair loss at 12.22%. Middle age (OR: 2.353, 95%CI: 1.171 ~ 4.729), underlying diseases (OR: 2.293, 95%CI: 1.216 ~ 4.324), severe key symptom (OR: 6.168, 95%CI: 1.376 ~ 27.642) and at least one other symptom (OR: 1.847, 95%CI: 1.225 ~ 2.718)during the recovery were the risk factors of poor overall health after infection (current overall health score

Abstract Primary cilia are present on renal tubules and are implicated to play a pivotal role in transducing signals during development; however, the oncogenic role of cilia in clear cell renal cell carcinoma (ccRCC) has not been examined. Here we show that VHL wild-type ccRCC cell lines have a high incidence of primary cilia, and a high frequency of primary cilia is positively correlated with VHL expression and poor prognosis. Besides, the depletion of KIF3A and IFT88, genes required for ciliogenesis, significantly inhibited tumor proliferation and metastasis in vitro and in vivo. Further analysis found that mutations of key genes in hedgehog signaling are enriched in VHL wild ccRCC, its downstream signaling activation depends on ciliogenesis. Moreover, depletion of primary cilia or suppression of hedgehog pathway activation with inhibitor-induced robust autophagic cell death. Collectively, our findings revealed that primary cilia could serve as a diagnostic tool and provide new insights into the mechanism of VHL wild-type ccRCC progression. Targeting the primary cilia-hedgehog pathway may represent an effective therapeutic strategy for VHL wild-type ccRCC.

Abstract Background Therapeutic approaches that combine conventional photodynamic therapy (PDT) with gas therapy (GT) to sensitize PDT are an attractive strategy, but the molecular structure design of the complex lacks effective guiding strategies. Results Herein, we have developed a nanoplatforms Cy-NMNO@SiO2 based on mesoporous silica materials loaded NIR-activatable small-molecule fluorescent probe Cy-NMNO for the synergistic treatment of photodynamic therapy/gas therapy (PDT/GT) in antibacterial and skin cancer. The theoretical calculation results showed that the low dissociation of N-NO in Cy-NMNO enabled it to dissociate effectively under NIR light irradiation, which is conducive to produce Cy and NO. Cy showed better 1O2 generation performance than Cy-NMNO. The cytotoxicity of Cy-NMNO obtained via the synergistic effect of GT and PDT synergistically enhances the effect of photodynamic therapy, thus achieving more effective tumor treatment and sterilization than conventional PDT. Moreover, the nanoplatforms Cy-NMNO@SiO2 realized efficient drug loading and drug delivery. Conclusions This work not only offers a promising approach for PDT-GT synergistic drug delivery system, but also provides a valuable reference for the design of its drug molecules. Graphical Abstract

Abstract Background Deletion or duplication in the DMD gene is one of the most common causes of Duchenne and Becker muscular dystrophy (DMD/BMD). However, the pathogenicity of complex rearrangements involving DMD, especially segmental duplications with unknown breakpoints, is not well understood. This study aimed to evaluate the structure, pattern, and potential impact of rearrangements involving DMD duplication. Methods Two families with DMD segmental duplications exhibiting phenotypical differences were recruited. Optical genome mapping (OGM) was used to explore the cryptic pattern of the rearrangements. Breakpoints were validated using long-range polymerase chain reaction combined with next-generation sequencing and Sanger sequencing. Results A multi-copy duplication involving exons 64–79 of DMD was identified in Family A without obvious clinical symptoms. Family B exhibited typical DMD neuromuscular manifestations and presented a duplication involving exons 10–13 of DMD. The rearrangement in Family A involved complex in-cis tandem repeats shown by OGM but retained a complete copy (reading frame) of DMD inferred from breakpoint validation. A reversed insertion with a segmental repeat was identified in Family B by OGM, which was predicted to disrupt the normal structure and reading frame of DMD after confirming the breakpoints. Conclusions Validating breakpoint and rearrangement pattern is crucial for the functional annotation and pathogenic classification of genomic structural variations. OGM provides valuable insights into etiological analysis of DMD/BMD and enhances our understanding for cryptic effects of complex rearrangements.

Abstract Background Microwave ablation (MWA) is widely used to eliminate colorectal liver metastases (CRLM). However, the risk of tumor recurrence is difficult to predict due to lack of reliable clinical and biological markers. Elevation of gamma-glutamyl transferase (GGT) and aspartate transaminase (AST) provides signals for liver inflammation and cancer progression. The present study evaluated the association between pre-ablation GGT to AST ratio index (GSR) and hepatic recurrence in patients with CRLM after MWA. Methods A retrospectively analyzed 192 CRLM patients who underwent MWA from January 2013 to December 2017. Pre-ablation GSR was classified into high (≤ 2.34) or low (> 2.34) using the upper quartile value. The prognostic value of GSR and other risk factors for liver progression-free survival (LPFS) and cancer-specific survival (CSS) were evaluated by univariate and multivariate analyses. Results High GSR was significantly associated with males (P = 0.041), the presence of cholelithiasis (P = 0.012), but not pre-ablation chemotherapy (P = 0.355), which caused significantly increased levels of GGT (P = 0.015) and AST (P = 0.008). GSR showed a significant association with LPFS and CSS through univariate analysis (P = 0.002 and 0.006) and multivariate analysis (P = 0.043 and 0.037). The subgroup analysis demonstrated no interaction between GSR and all variables except for distribution in the sub-analysis of LPFS. Conclusions Our findings suggest that the pre-ablation GSR can be considered as a promising prognostic indicator for poor prognosis of patients with CRLM underwent MWA. Trial registration Not applicable.

Abstract There is still room for improvement in first-line treatment of advanced small cell lung cancer (SCLC). This trial firstly investigated efficacy and safety of antiangiogenic therapy (surufatinib) (200 mg, qd, po) plus anti-PD-1 treatment (toripalimab) (240 mg, d1, ivdrip) combined with etoposide (100 mg/m², d1-d3, iv, drip) and cisplatin (25 mg/m², d1-d3, ivdrip) for advanced SCLC as first-line treatment, which has been registered on ClinicalTrials.gov under the identifier NCT04996771. The four-drug regimen was conducted q3w for 4 cycles with maintenance therapy of surufatinib and toripalimab. The primary endpoint was progression-free survival (PFS). The secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. All of the 38 patients were enrolled for safety analysis, while only 35 patients were enrolled for efficacy analysis since loss of efficacy evaluation in 3 cases after treatment. After a median follow-up of 21.3 months, the ORR was 97.1% (34/35), and the DCR and the tumor shrinkage rate were both 100% (35/35). The median PFS was 6.9 months (95% CI: 4.6 m–9.2 m) and the median OS was 21.1 months (95% CI: 12.1 m–30.1 m). The 12-month, 18-month, and 24-month OS rates were 66.94%, 51.39% and 38.54%. The occurrence rate of grade ≥3 treatment-emergent adverse events (TEAEs) was 63.2% (24/38), including neutrophil count decreased (31.6%, 12/38), white blood cell count decreased (23.7%, 9/38) and platelet count decreased (10.5%, 4/38). No unexpected adverse events occurred. This novel four-drug regimen (surufatinib, toripalimab, etoposide plus cisplatin) revealed impressive therapeutic efficacy and tolerable toxicities.

Abstract Background Plants that contain brewing microorganisms are used in traditional fermentation starters, which are an essential part of local diet, nutrition, life, and health. Regionally, the plant species used and the microorganisms included in traditional fermentation starters are diverse, endowing local fermented drinks with different flavors and health benefits. However, related traditional knowledge has been scarcely documented or revealed. Methods An ethnobotanical survey was conducted in five towns of Nayong County in northwestern Guizhou, China. Snowball sampling, semi-structured interviews, free lists, and participatory observation were used to collect information on Jiuqu Plants (JPs) and jiuqu-making techniques. The PacBio platform was used to study the microbial community structure and diversity in the Chuanqing people’s jiuqu. Results In total, 225 informants were interviewed, including 116 who provided plants and technological processes for making Chinese baijiu jiuqu (CBJ) and 139 who provided information about making fermented glutinous rice jiuqu (FGRJ). This study found that older people have more abundant knowledge about CBJ plants. Poaceae was found to be the dominant family used in making CBJ and FGRJ (7 species each). Compared to individual plant parts, the whole plant is most commonly used in two kinds of jiuqu (19.5% in CBJ and 22.6% in FGRJ). The Chuanqing people’s jiuqu is used to treat dietary stagnation and indigestion. The highest relative frequency of citation of the CBJ plant was Ficus tikoua Bureau, and the counterpart of the FGRJ plant was Buddleja macrostachya Benth. The dominant bacterial species in jiuqu were Gluconobacter japonicus (YQ1, YQ4) and Pediococcus pentosaceus (YQ2, YQ3), and the dominant fungal species was Rhizopus oryzae. Conclusion For the first time, this study documents the unique traditional jiuqu knowledge and reveals the microbial mystery behind the FGRJ of the Chuanqing people. Therefore, this study encourages the use of online social media platforms in order to spread Jiuqu culture, the use of the new media wave in order to create multimedia databases, and also suggests that local communities should develop preservation intervention programs, in addition to nurturing the inheritors in order to prevent the disappearance of traditional Jiuqu knowledge. This research contributes to the conservation and demystification of the traditional jiuqu knowledge of the Chuanqing people and lays the foundation for further research on its microbiology, nutrition, and metabolomics.

Abstract Lipid nanoparticles (LNPs) are currently the most commonly used non-viral gene delivery system. Their physiochemical attributes, encompassing size, charge and surface modifications, significantly affect their behaviors both in vivo and in vitro. Nevertheless, the effects of these properties on the transfection and distribution of LNPs after intramuscular injection remain elusive. In this study, LNPs with varying sizes, lipid-based charges and PEGylated lipids were formulated to study their transfection and in vivo distribution. Luciferase mRNA (mLuc) was entraped in LNPs as a model nucleic acid molecule. Results indicated that smaller-sized LNPs and those with neutral potential presented superior transfection efficiency after intramuscular injection. Surprisingly, the sizes and charges did not exert a notable influence on the in vivo distribution of the LNPs. Furthermore, PEGylated lipids with shorter acyl chains contributed to enhanced transfection efficiency due to their superior cellular uptake and lysosomal escape capabilities. Notably, the mechanisms underlying cellular uptake differed among LNPs containing various types of PEGylated lipids, which was primarily attributed to the length of their acyl chain. Together, these insights underscore the pivotal role of nanoparticle characteristics and PEGylated lipids in the intramuscular route. This study not only fills crucial knowledge gaps but also provides significant directions for the effective delivery of mRNA via LNPs. Graphical Abstract

Abstract Despite the importance of cellular senescence in human health, how damaged cells undergo senescence remains elusive. We have previously shown that promyelocytic leukemia nuclear body (PML-NBs) translocation of the ciliary FBF1 is essential for senescence induction in stressed cells. Here we discover that an early cellular event occurring in stressed cells is the transient assembly of stress-induced nucleus-to-cilium microtubule arrays (sinc-MTs). The sinc-MTs are distinguished by unusual polyglutamylation and unique polarity, with minus-ends nucleating near the nuclear envelope and plus-ends near the ciliary base. KIFC3, a minus-end-directed kinesin, is recruited to plus-ends of sinc-MTs and interacts with the centrosomal protein CENEXIN1. In damaged cells, CENEXIN1 co-translocates with FBF1 to PML-NBs. Deficiency of KIFC3 abolishes PML-NB translocation of FBF1 and CENEXIN1, as well as senescence initiation in damaged cells. Our study reveals that KIFC3-mediated nuclear transport of FBF1 along polyglutamylated sinc-MTs is a prerequisite for senescence induction in mammalian cells.

Abstract TIMM9 has been identified as a mediator of essential functions in mitochondria, but its association with pan-cancer is poorly understood. We herein employed bioinformatics, computational chemistry techniques and experiments to investigate the role of TIMM9 in pan-cancer. Our analysis revealed that overexpression of TIMM9 was significantly associated with tumorigenesis, pathological stage progression, and metastasis. Missense mutations (particularly the S49L variant), copy number variations (CNV) and methylation alterations in TIMM9 were found to be associated with poor cancer prognosis. Moreover, TIMM9 was positively related with cell cycle progression, mitochondrial and ribosomal function, oxidative phosphorylation, TCA cycle activity, innate and adaptive immunity. Additionally, we discovered that TIMM9 could be regulated by cancer-associated signaling pathways, such as the mTOR pathway. Using molecular simulations, we identified ITFG1 as the protein that has the strongest physical association with TIMM9, which show a promising structural complement.

Abstract Background Breakthrough cancer pain (BTcP) has a negative impact on patients’ quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25μg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients. Methods The trial was conducted in opioid-tolerant cancer patients with 1 ~ 4 BTcP outbursts per day. Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations, with an interval of at least 4 min between doses. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 min (SPID30). Results A total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes (p

ObjectiveA local dynamic collision avoidance algorithm based on an improved fast-marching square (IFMS) method is proposed to solve the multi-vessel collision avoidance problem of unmanned sailboats in open water. MethodsConsidering the uncontrollable speed of a sailboat, its collision avoidance behavior is transformed into a heading control problem, with the direction of the total potential field gradient decreasing as the desired collision avoidance heading. When sailing without risk of collision or downwind, a temporal potential field is constructed to avoid all stationary irregular obstacles and reach the target point. When the sailboat has sailing constraints, Gaussian likelihood functions are designed for specific encounter situations to dynamically construct obstacle potential fields according to the convention on the international regulations for preventing collisions at sea (COLREGS), while the local wind potential field is introduced to consider the dead zone of a sailboat and realize the application requirements of combining dynamic collision avoidance with a zigzag sailing strategy. ResultsThe results show that the proposed algorithm can enable an unmanned sailboat to successfully achieve collision avoidance operations with other sailboats and restricted motor vessels in various encounter situations, while complying with collision avoidance rules and avoiding navigational dead zones. Compared with the original fast-marching square (FMS) algorithm, the upwind sailing time is significantly reduced and the planned collision avoidance trajectory is safer and more reasonable.ConclusionThe proposed method complies with the characteristics of sailboat motion and collision avoidance rules, has high safety and robustness in complex environments, and possesses scientific value regarding the development of autonomous obstacle avoidance technology for unmanned sailboats.

Abstract Sprint interval training (SIT) is a potent exercise strategy to enhance athletes’ anaerobic capacity in a time-efficient manner. This study aimed to investigate the impact of low-volume, court-based SIT on the anaerobic capacity and sport-specific performance in competitive tennis players. Twenty-four competitive collegiate tennis players were randomly assigned to either the SIT group (n = 12; three sessions per week of court-based repeated-sprint training) or the traditional endurance training (ET) group (n = 12; three sessions per week of 45-min continuous treadmill running, n = 12) for a 6-weeks intervention. Baseline and post-intervention assessments included the Wingate Anaerobic Test, elimination rate of blood lactate (BLAer), tennis-specific repeated sprint ability (RSA), and the Yo-Yo Intermittent Recovery Test Level 2 (YoYo-IR2). The results showed that SIT group demonstrated significant improvements in peak and average power during the Wingate test (p = 0.07; p

Abstract The free-field switching of the perpendicular magnetization by the out-of-plane polarized spin current induced spin-orbit torque makes it a promising technology for developing high-density memory and logic devices. The materials intrinsically with low symmetry are generally utilized to generate the spin current with out-of-plane spin polarization. However, the generation of the out-of-plane polarized spin current by engineering the symmetry of materials has not yet been reported. Here, we demonstrate that paramagnetic CaRuO3 films are able to generate out-of-plane polarized spin current by engineering the crystal symmetry. The non-uniform oxygen octahedral tilt/rotation along film’s normal direction induced by oxygen octahedral coupling near interface breaks the screw-axis and glide-plane symmetries, which gives rise to a significant out-of-plane polarized spin current. This spin current can drive field-free spin-orbit torque switching of perpendicular magnetization with high efficiency. Our results offer a promising strategy based on crystal symmetry design to manipulate spin current and could have potential applications in advanced spintronic devices.

Abstract Background Breastfeeding has many benefits for mothers and infants. Lactogenesis II is one of the key steps in the implementation of breastfeeding. If lactogenesis II occurs more than 72 h after delivery, it is termed delayed onset of lactation (DOL). DOL is associated with decreased milk production, shortened breastfeeding time, and pathological neonatal weight loss. A comprehensive summary of the incidence and factors influencing DOL is needed to provide a basis for improving breastfeeding practices and health outcomes. Methods Studies on the incidence and factors influencing DOL were retrieved from 13 Chinese and English databases (PubMed, Embase, Web of Science, Cochrane Library, CINAHL, etc.) from database inception to August 2023. Two researchers independently conducted the study screening, data extraction and quality evaluation. Stata 16.0 SE software was used for data analysis, and sensitivity analysis and publication bias tests were also performed. The qualitative description method was used to analyse studies that could not be combined quantitatively. Results A total of 35 studies involving 19,176 parturients, including 4,922 who had DOL, were included. The mean Newcastle‒Ottawa scale score of the included studies was ≥ 6, indicating that the quality was relatively high. Finally, the incidence of DOL was 30%, and 13 factors influencing DOL with robust results and no publication bias were obtained: prepregnancy body mass index (overweight or obesity), gestational diabetes, gestational hypertension, thyroid disease during pregnancy, serum albumin levels (

Abstract Eleocharis dulcis (Burm. f.) Trin. ex Hensch., commonly known as Chinese water chestnut, is a traditional aquatic vegetable in China, and now is widely cultivated throughout the world because of its high nutritional value and unique tastes. Here, we report the assembly of a 493.24 Mb telomere-to-telomere (T2T) genome of E. dulcis accomplished by integrating ONT ultra-long reads, PacBio long reads and Hi-C data. The reference genome was anchored onto 111 gap-free chromosomes, containing 48.31% repeat elements and 33,493 predicted protein-coding genes. Whole genome duplication (WGD) and inter-genomic synteny analyses indicated that chromosome breakage and genome duplication in E. dulcis possibly occurred multiple times during genome evolution after its divergence from a common ancestor with Rhynchospora breviuscula at ca. 35.6 Mya. A comparative time-course transcriptome analysis of corm development revealed different patterns of gene expression between cultivated and wild accessions with the highest number of differentially expressed genes (DEGs, 15,870) at the middle swelling stage and some of the DEGs were significantly enriched for starch metabolic process.

Acute pancreatitis (AP) is a potentially fatal condition with no targeted treatment options. Although inhibiting xanthine oxidase (XO) in the treatment of AP has been studied in several experimental models and clinical trials, whether XO is a target of AP and what its the main mechanism of action is remains unclear. Here, we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP. We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models. We also found that allopurinol and febuxostat, as purine-like and non-purine XO inhibitors, respectively, exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points. Moreover, we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity. Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha (HIF-1α)-regulated lactate dehydrogenase A (LDHA) and NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathways and reduced the enrichment of 13C6-glucose to 13C3-lactate. Lastly, we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels, while pancreatic XO and urate were also increased in severe AP patients. These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.

Abstract Objective To determine the prevalence of and risk factors for overweight and obese among Chinese children and adolescents. Methods This analytical cross-sectional study included 16,640 children and adolescents aged 6–18 years across four provinces of China in 2016. Physical characteristics and responses to questionnaires were analyzed. Body Mass Index (BMI) and the prevalence of overweight and obesity were calculated. Results Among children and adolescents, the overall prevalence of overweight and obesity in 2016 in four regions of China was 27.2% and 29.6%, respectively. Among different stages and sexes, the highest prevalence of obesity (15.8%) was observed in adolescent boys. From childhood to adolescence, the obesity rate among boys increased by 0.7% (from 15.1% to 15.8%), while the obesity rate among girls decreased by 0.9% (from 10.8% to 9.9%). Children and adolescents who were overweight or obese had significantly higher systolic blood pressures, larger waist circumferences and larger hip sizes than those with a normal BMI. Logistic regression analyses identified thirteen factors associated with overweight or obesity in children and adolescents. Conclusions Our results indicate that the prevalence of overweight and obesity is high among children and adolescents, especially among male adolescents in four regions of China. A suitable intervention program should not only help parents understand the serious risk of childhood obesity but also, more importantly, help to encourage a healthy lifestyle among children and adolescents.

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. Methods We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. Results A functional assay identified that transforming growth factor-β1 (TGF-β1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. Conclusions These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.

Abstract Fractional quantum Hall (FQH) states are exotic quantum many-body phases whose elementary charged excitations are anyons obeying fractional braiding statistics. While most FQH states are believed to have Abelian anyons, the Moore–Read type states with even denominators – appearing at half filling of a Landau level (LL) – are predicted to possess non-Abelian excitations with appealing potential in topological quantum computation. These states, however, depend sensitively on the orbital contents of the single-particle LL wavefunctions and the LL mixing. Here we report magnetotransport measurements on Bernal-stacked trilayer graphene, whose multiband structure facilitates interlaced LL mixing, which can be controlled by external magnetic and displacement fields. We observe robust FQH states including even-denominator ones at filling factors ν = − 9/2, − 3/2, 3/2 and 9/2. In addition, we fine-tune the LL mixing and crossings to drive quantum phase transitions of these half-filling states and neighbouring odd-denominator ones, exhibiting related emerging and waning behaviour.

Abstract Background The modifiable mechanisms underlying the association between socioeconomic status (SES) and preterm birth remain unclear. This study aimed to investigate the relationship between preterm birth and maternal SES or gestational weight gain (GWG), as well as the role of GWG in mediating SES disparities in preterm birth. Methods Data was from a hospital-based sub-study of physical growth and development survey for Chinese newborns with various gestational ages. Singleton newborns aged from 24 to 42weeks’ gestation and their mothers were included. Using information from maternal questionnaire, a composite SES was constructed with parental education and family annual income. GWG as mediator was calculated by deducting pre-pregnancy weight from maternal weight at delivery. Logistic regression model was adopted to investigate the association of preterm birth with SES or GWG. Causal mediation analysis was performed to measure mediating effect of GWG on the pathway from SES to preterm birth. Results After controlling for potential confounders, risk of preterm birth was reduced by 12.4% (OR = 0.876, 95%CI:0.855–0.879) for per one-kilogram increase of GWG, and risk of preterm birth was reduced by 24% (OR = 0.760, 95%CI: 0.717–0.806) for per one-unit increase of SES score. Mediation analysis supported a significant association between higher SES and decreased risk of preterm partly through higher GWG, in which estimated proportion mediated by GWG was 13.04% (95%CI: 11.89–16.25). GWG also played a significant role as a mediator when socioeconomic status was indicated by maternal education, paternal education or family income. GWG mediated approximately 11.03% (95% CI: 8.56–18.25) of the total effect of SES on very preterm birth, which was greater than that for moderate preterm birth (6.72%, 95%CI: 2.72–31.52) and late preterm birth (9.04%, 95%CI: 5.24–24.04). A series of sensitive analysis confirmed the robustness of association of interest. Conclusion Increased GWG and higher socioeconomic status are strongly associated with a lower risk of preterm birth. GWG mediates socioeconomic disparities in preterm birth, most notably in very preterm birth. Understanding this mechanism will aid in the development of interventions and policy for maternal and child health care.

Abstract Objective To reveal the contributing effects of MTDH gene SNPs in the risk of invasive ductal breast cancer (IDC). Patients and methods A case–control study was conducted, recruiting a total of 300 cases of IDC and 565 cancer-free controls from East China. Genotyping of three single-nucleotide polymorphisms (SNPs) in the MTDH gene was performed. Genomic DNA was extracted from peripheral blood samples of patients. The three SNPs (rs1311 T > C, rs16896059 G > A, rs2449512 A > G) in the MTDH gene were selected for detection using a TaqMan real-time polymerase chain reaction assay. The association between MTDH and the risk of IDC was analyzed employing an epidemiology case–control study and a multinomial logistic regression model. Results Among the three evaluated SNPs, rs1311 T > C, rs16896059 G > A, and rs2449512 A > G demonstrated a significant association with an increased risk of IDC. Furthermore, stratified analysis revealed that individuals carrying the rs1311 CC genotype, rs16896059 GA/AA genotypes, and rs2449512 GG genotype were more susceptible to developing IDC in subgroups of patients younger than 53 years, without family history of IDC, pre-menopause status, clinical stage 2, high grade, with no distant metastasis or invasion, Her2-positive type, ER positive, PR positive, and Ki67 cells less than 10%. However, carriers of the rs16896059 GA/AA genotypes and rs2449512 GG genotype had an elevate the risk of IDC in patients with tumor size larger than 2 cm, post-menopause status, clinical stage 3, with invasion, lymph node infiltration, ER negative, PR negative, Her2 negative, and Ki67 cells exceeding 10%. Compared to the reference haplotype TGA, haplotypes TAA, TAG, and TGG were significantly associated with an increased IDC risk. Conclusion In this study, we demonstrated a significant association between MTDH gene polymorphisms and an increased risk of IDC. Moreover, our findings suggested that MTDH gene polymorphisms could serve as a potential biomarker for IDC subtyping and therapeutic selection.

Purpose: To determine whether the overexpression of the Argonaute RNA-induced silencing complex catalytic component 2 (Ago2) improves erectile function in mice after cavernous nerve injury (CNI). Materials and Methods: Lentiviruses containing Ago2 open reading frame (ORF) mouse clone (Ago2 O/E) were used to overexpress Ago2, and lentiviruses ORF negative control particles (NC) were used as a negative control. Three days before preparing the CNI model, we injected lentiviruses into the penises of 8-week-old male C57BL/6 mice. Animals were then divided into four groups: the sham operation control group and the CNI+phosphate-buffered saline, CNI+NC, and CNI+Ago2 O/E groups. One week later, erectile function was assessed by electrically stimulating cavernous nerves bilaterally and obtaining intracavernous pressure parameters. Penile tissue was also collected for molecular mechanism studies. Results: Ago2 overexpression improved erectile function in mice after CNI-induced erectile dysfunction (ED). Immunofluorescence staining and Western blot analysis showed that under Ago2 overexpressing conditions, the contents of endothelial cells, pericytes, and neuronal cells increased in the penile tissues of CNI mice, and this was attributed to reduced apoptosis and ROS production. In addition, we also found that Ago2 overexpression could restore penile mitochondrial function, thereby improving erectile function in CNI-induced ED mice. Conclusions: Our findings demonstrate that Ago2 overexpression can reduce penile cell apoptosis, restore penile mitochondrial function, and improve erectile function in CNI-induced ED mice.

Abstract Purpose Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials. Methods Patients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined “EBV response” as 3 consecutive timepoints of load below 50% of baseline, and “EBV progression” as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples. Results We found that the baseline EBV DNA load was positively correlated with tumor size (spearman p

AIM: To examine the regulatory role of microRNA-204 (miR-204) on silent information regulator 1 (SIRT1) and vascular endothelial growth factor (VEGF) under high-glucose-induced metabolic memory in human retinal pigment epithelial (hRPE) cells. METHODS: Cells were cultured with either normal (5 mmol/L) or high D-glucose (25 mmol/L) concentrations for 8d to establish control and high-glucose groups, respectively. To induce metabolic memory, cells were cultured with 25 mmol/L D-glucose for 4d followed by culture with 5 mmol/L D-glucose for 4d. In addition, exposed in 25 mmol/L D-glucose for 4d and then transfected with 100 nmol/L miR-204 control, miR-204 inhibitor or miR-204 mimic in 5 mmol/L D-glucose for 4d. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect miR-204 mRNA levels. SIRT1 and VEGF protein levels were assessed by immunohistochemical and Western blot. Flow cytometry was used to investigate apoptosis rate. RESULTS: It was found that high glucose promoted miR-204 and VEGF expression, and inhibited SIRT1 activity, even after the return to normal glucose culture conditions. Upregulation of miR-204 promoted apoptosis inhibiting SIRT1 and increasing VEGF expression. However, downregulation of miR-204 produced the opposite effects. CONCLUSION: The study identifies that miR-204 is the upstream target of SIRT1and VEGF, and that miR-204 can protect hRPE cells from the damage caused by metabolic memory through increasing SIRT1 and inhibiting VEGF expression.

Background Leptomeningeal collateral status is a major determinant of outcomes in patients with acute ischemic stroke; however, the factors that determine collateral status are not well understood. We conducted a comprehensive systematic review and meta‐analysis to identify determinants associated with collateral status in patients with anterior circulation infarction. Methods and Results The PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched for studies that reported the determinants of leptomeningeal collateral status in acute ischemic stroke between January 2000 and June 2023. A random‐effects meta‐analysis model was used to pool the determinants of leptomeningeal collateral status. Eighty‐one studies with 17 366 patients met the inclusion criteria. We analyzed 31 potential risk factors, and the results indicated that worse leptomeningeal collateral status was significantly associated with older age (weighted mean difference, 1.22 [95% CI, 0.69 to 1.76]), male sex (odds ratio [OR], 1.12 [95% CI, 1.02 to 1.23]), hypertension (OR, 1.27 [95% CI, 1.15 to 1.40]), diabetes (OR, 1.21 [95% CI, 1.10 to 1.33]), atrial fibrillation (OR, 1.26 [95% CI, 1.09 to 1.46]), cardioembolic stroke (OR, 1.27 [95% CI, 1.04 to 1.55]), internal carotid artery occlusion (OR, 1.84 [95% CI, 1.50 to 2.25]), and higher admission blood glucose (weighted mean difference, 8.74 [95% CI, 2.52 to 18.51]). Conclusions Hypertension and diabetes could be modifiable risk factors associated with leptomeningeal collateral status. Older age and male sex could be nonmodified risk factors. Further high‐quality therapeutic studies focusing on controlling risk factors are needed to support our findings.

Objective: Activating brown adipose tissue (BAT) thermogenesis is a promising approach to combat obesity and metabolic disorders. The post-transcriptional regulation of BAT thermogenesis mediated by RNA-binding proteins (RBPs) is still not fully understood. This study explores the physiological role of novel RBPs in BAT differentiation and thermogenesis. Methods: We used multiple public datasets to screen out novel RBPs responsible for BAT differentiation and thermogenesis. In vitro loss- and gain-of-function experiments were performed in both C3H10T1/2 preadipocytes and mature brown adipocytes to determine the role of Y-box binding protein 3 (YBX3) in brown adipocyte differentiation and thermogenesis. Adeno-associated virus (AAV)-mediated BAT-specific knockdown or overexpression of Ybx3 was applied to investigate the function of YBX3 in vivo. Results: YBX3 is a brown adipocyte-enriched RBP induced by cold stimulation and β-adrenergic signaling. Both in vitro loss- and gain-of-function experiments demonstrate that YBX3 is essential for brown adipocyte differentiation and thermogenesis. BAT-specific loss of Ybx3 dampens thermogenesis and exacerbates diet-induced obesity in mice, while overexpression of Ybx3 promotes thermogenesis and confers protection against diet-induced metabolic dysfunction. Transcriptome analysis and mitochondrial stress test indicate that Ybx3 deficiency compromises the mitochondrial oxidative phosphorylation, leading to thermogenic failure. Mechanistically, YBX3 stabilizes the mRNA of Slc3a2 and Pparg, which facilitates branched-chain amino acid (BCAA) influx and catabolism and fuels brown adipocyte differentiation and thermogenesis. Conclusions: YBX3 facilitates BAT fueling BCAA to boost thermogenesis and energy expenditure, which protects against obesity and metabolic dysfunction. Thus, YBX3 could be a promising therapeutic target for obesity.

Objective This prospective observational study aims to demonstrate the clinical efficacy of dienogest in treating endometriomas with a maximum diameter of ≥4 cm.Methods Patients (n = 81) with endometriomas (diameter of ≥4 cm) were enrolled and administered orally with dienogest (2 mg daily) and followed up for a year [Ethical approval code: 2020 Research 343]. Further, the efficacy was determined by recording the largest diameter and volume of the endometriomas, uterine volume, endometrial thickness, and the largest diameter of uterine fibroids in the patients during 0, 6, and 12 months. The pain symptoms were assessed using the Numerical Rating Scale (NRS), and the side effects of medication were monitored. With the consent, some patients underwent routine blood tests, and serum hormone, as well as Anti-Müllerian Hormone (AMH) levels were measured.Results The dienogest treatment resulted in a significant reduction of the maximum diameter of these cysts from 50.5 mm to 41 mm in 6 months and 34 mm in 12 months. In addition, the volume of the cysts significantly decreased from 37.8 ml from baseline to 18.5 ml in 6 months and 11.8 ml in 12 months. Among 26 subjects with ultrasonic signs of endometrial polyps, 92.3% of cases displayed no polyps after 12 months. No significant changes were observed in the size of uterine fibroids and AMH levels. The NRS score showed a decrease from an average of 6.6–1.2 in 12 months.Conclusion Dienogest could effectively reduce the diameter and volume of endometriomas with a maximum diameter of ≥4 cm, improving anemia, as well as pain symptoms and preserving ovarian function.

Objective The relationship between serum total cholesterol (TC) and triglyceride (TG) levels and mortality in maintenance hemodialysis (MHD) patients remains inconsistent. We aimed to explore the individual and combined association of TC and TG levels with the risk of mortality in Chinese MHD patients.Methods 1036 MHD patients were enrolled in this multicenter, prospective cohort study. The serum levels of total cholesterol and triglycerides were measured at baseline. The primary outcome was all-cause mortality and secondary outcome was cardiovascular disease (CVD) mortality.Results During a median follow-up duration of 4.4 years (IQR= 2.0–7.9 years), 549 (53.0%) patients died, and 297 (28.7%) deaths were attributed to CVD. Compared with patients with TC levels in the first three quartiles (

ABSTRACTThe waning of maternal antibodies may cause infants to lose protection against measles before receiving measles-containing vaccine (MCV). The aim of this study is to investigate the changing characteristics and influencing factors of measles antibodies in preterm infants (PT), and to provide scientific basis for optimizing MCV vaccination strategy of the target population. Blood samples were collected from PT and full-term infants (FT) at the chronological age (CA) of 3, 6, and 12 months. Measles antibodies were quantitatively detected by enzyme-linked immunosorbent assay. Demographic and vaccination information were both collected. Kruskal–Wallis rank sum test was used to compare the measles antibodies among different gestation age (GA) groups, and multiple linear regression was performed to identify the correlative factors for the antibodies. Measles antibodies of PT decreased significantly with age increasing before MCV vaccination. The positive rates of antibodies of PT were 10.80% and 3.30% at the age of 3 and 6 months, respectively (p

ABSTRACTDespite the high effectiveness of HPV vaccines in preventing infection, vaccine hesitancy remains a concern, particularly in China. This study aimed to explore college students’ attitudes toward HPV vaccination and identify associated factors. Data was collected through a cross-sectional survey using self-administered questionnaires in four cities from May to June 2022. Chi-square tests and logistic regression analyses were conducted to identify factors. Additionally, an integrated structural equation model (SEM) based on the 3Cs (confidence, convenience, complacency) was developed to understand underlying factors contributing to hesitancy. The results from 2261 valid questionnaires were enlightening. A significant 89.47% (59.4% for females) considered HPV vaccination necessary, with 9.82% remaining neutral and only 0.71% deeming it unnecessary. Factors like higher education, being a medical student, residing in urban areas, having medical insurance, more extraordinary living expenses, a family history of tumors, and a solid understanding of HPV played a role in perceiving the vaccine as necessary. Among the 1438 female respondents, 84.36% had no hesitancy toward HPV vaccination, 13.53% expressed hesitancy, and 2.11% refused vaccination. Factors like age, understanding of HPV, medical staff recommendations, living expenses, and family history influenced hesitancy levels. SEM revealed that the 3Cs significantly affected vaccine hesitancy. Factors like price, booking process, vaccination times, trust in vaccines, medical staff recommendations, efficiency, and risk perception collectively influenced hesitancy. In conclusion, this study found high acceptance of HPV vaccination but acknowledged the complexity of hesitancy factors. It recommends medical staff disseminate scientific knowledge, offer recommendations, simplify booking procedures, and expand vaccination sites to address vaccine hesitancy effectively.

BackgroundAllergic rhinitis (AR) affects up to 40% of the population, leading to significant healthcare expenditures. Current mainstream treatments, while effective, can lead to side effects and do not address the underlying immunological imbalances. Zingiberis Rhizoma Carbonisatum (ZRC), the partially charred product of Zingiberis Rhizoma (ZR), has been widely used clinically in China since ancient times to treat respiratory disorders.MethodsInspired by the similarity between high-temperature pyrolysis and carbonization processing of herbal medicine, ZRC derived CDs (ZRC-CDs) were extracted and purified through several procedures. Then, the physicochemical characteristics of CDs were delineated through a suite of characterization methods. Moreover, our investigation zeroed in on elucidating the ameliorative impacts of CDs on ovalbumin-induced rat models alongside their underlying mechanisms.ResultsZRC-CDs with particle sizes ranging from 1.0 to 3.5 nm and rich surface functional groups. Additionally, we observed that ZRC-CDs significantly attenuated nasal symptoms and pathological damage in ovalbumin-induced AR rats, and modulated lipid metabolism and type 2 inflammatory responses. They also inhibit PI3K/AKT and JAK/STAT pathways, which are associated with metabolism and inflammation. Importantly, ZRC-CDs demonstrated high biocompatibility, underscoring their potential as a novel therapeutic agent.ConclusionZRC-CDs offer a promising alternative for AR treatment and could help facilitate broader clinical use of the ZRC. In addition, the exploration of the inherent bioactivity of CDs can help to broaden their biological applications.

Abstract Background and Aims This network meta‐analysis aimed to compare the perioperative efficacy of various minimally invasive hysterectomy procedures for treating benign gynecological diseases and to assess whether vaginal natural orifice transluminal endoscopic hysterectomy (VNOTEH), a recently emerging procedure, is inferior to traditional laparoscopy. Methods We searched PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), Wanfang Data, and China VIP Database from inception to August 2022 and updated in June 2023. We included randomized controlled trials (RCTs) comparing different minimally invasive hysterectomy techniques in patients with benign gynecological conditions. The intervention measures included nine minimally invasive hysterectomies. The two researchers used the Cochrane risk‐of‐bias assessment tool for study appraisal. All statistical analyses and drawings were performed using STATA 17.0 and R 4.4.1. A network meta‐analysis (NMA) was conducted to compare the effectiveness of minimally invasive hysterectomy and rank its relative impact probabilistically. Results A total of 78 RCTs involving 7640 patients and nine minimally invasive hysterectomy methods with 16 intervention combinations were included in this study. Among these, 2, 63, and 13 studies were deemed to have a low, medium, and high risk of bias, respectively. Based on the Surface Under the Cumulative Ranking (SUCRA) probability ranking results of NMA, laparoendoscopic single‐site surgery‐laparoscopic‐assisted vaginal hysterectomy (LESS‐LAVH) demonstrated superior outcomes in terms of complications, infections, and 24‐h postoperative pain scores. LAVH exhibited better performance in injuries and hospital stays, total laparoscopic hysterectomy showed the least blood loss, and vaginal hysterectomy had the shortest operation time. Conclusion LESS‐LAVH and LAVH are recommended options, if feasible. Meanwhile, VNOTEH can achieve comparable results to traditional laparoscopy but requires careful attention to the risk of injury and infection. Future research should aim to broaden the search scope by including high‐quality, large‐scale, multicenter RCTs.

Retinoblastoma is the most common type of eye tumor in infants and children. Current treatments for retinoblastoma include intravenous chemotherapy, intra-arterial chemotherapy, intravitreal chemotherapy, cryotherapy, radiotherapy, and surgery. However, these treatments come accompanied by adverse effects such as the toxic side effects of chemotherapeutic drugs, post-operative complications including blindness after surgery, or other complications caused by radiotherapy. Immunotherapy is more promising for its low toxicity on normal cells and effectively improves the quality of life of patients. Disialoganglioside (GD2), a sphingolipid expressed on the surface of retinoblastoma, is a potential therapeutic target for retinoblastoma. We summarized immunotherapeutic approaches for both preclinical studies and clinical trials of GD2. An anti-GD2 monoclonal antibody (Dinutuximab), which has been approved for the treatment of high-risk neuroblastomas, has shown promising efficacy in improving patients’ prognosis. Additionally, chimeric antigen receptors (CAR)-T therapy, GD2 vaccines and nanoparticles are also potential therapeutics. Finally, we discuss the prospects and current limitations of these immunotherapeutic approaches for treating retinoblastoma, as well as how to address these problems.

Focusing on the global garment supply chain, this article explores a third effect, apart from the country-of-origin and the host-country effects, that impact the employment relations of overseas Chinese companies. This paper is based on field research and interviews of 42 stakeholders in the Cambodia and Burmese garment industries, and employs thematic qualitative text analysis to examine the data, revealing three main findings: First, the compliance of Chinese overseas factories to labor standards is significantly affected by codes of conduct if these factories supply lead firms in the global garment supply chain. Second, if Chinese overseas factories do not supply lead firms in the global garment supply chain, their compliance to labor standards is significantly influenced by the country-of-origin effect. Third, the strength of regulations in the host country is an important factor that moderates the relationship between code-of-conduct effect and labor-standards compliance as well as the relationship between country-of-origin effect and labor-standards compliance by Chinese overseas factories.

IntroductionType 2 diabetes (T2D) is a metabolic disorder marked by disruptions in glucolipid metabolism, with numerous signaling pathways contributing to its progression. The liver, as the hub of glycolipid metabolism, plays a pivotal role in this context. Mulberry leaf (ML), a staple in traditional Chinese medicine, is widely utilized in the clinical management of T2D. Synthesizing existing literature with the outcomes of prior research, it has become evident that ML enhances glucose metabolism via multiple pathways.MethodsIn our study, we induced T2D in rats through a regimen of high-sugar and high-fat diet supplementation, coupled with intraperitoneal injections of streptozotocin. We subsequently administered the aqueous extract of ML to these rats and assessed its efficacy using fasting blood glucose levels and other diagnostic indicators. Further, we conducted a comprehensive analysis of the rats’ liver tissues using metabolomics and proteomics to gain insights into the underlying mechanisms.ResultsOur findings indicate that ML not only significantly alleviated the symptoms in T2D rats but also demonstrated the capacity to lower blood glucose levels. This was achieved by modulating the glucose-lipid metabolism and amino-terminal pathways within the liver. ACSL5, Dlat, Pdhb, G6pc, Mdh2, Cs, and other key enzymes in metabolic pathways regulated by ML may be the core targets of ML treatment for T2D.DiscussionMulberry leaf ameliorate STZ induced diabetic rat by regulating hepatic glycometabolism and fatty acid β-oxidation.

Abstract The dynamic interplay between parenchymal hepatocytes and non‐parenchymal cells (NPCs), such as macrophages, is an important mechanism for liver metabolic homeostasis. Although numerous endeavors have been made to identify the mediators of metabolic dysfunction associated steatohepatitis (MASH), the molecular underpinnings of MASH progression remain poorly understood, and therapies to arrest MASH progression remain elusive. Herein, it is revealed that the expression of grancalcin (GCA) is upregulated in the macrophages of patients and rodents with MASH and correlates with MASH progression. Notably, the administration of recombinant GCA aggravates the development of MASH, whereas, Gca deletion in myeloid cells blunts liver steatosis and inflammation in multiple MASH murine models. Mechanistically, GCA activates macrophages via TLR9‐NF‐κB signaling, and the activated macrophages promote hepatocyte lipid accumulation and apoptosis via secretion of Interleukin‐6(IL‐6), Tumor Necrosis Factor α (TNFα), and Interleukin‐1β(IL‐1β), thereby leading to hepatic steatosis and inflammation. Finally, the therapeutic administration of antibody blocking GCA effectively halts the progression of MASH. Collectively, these findings implicate GCA as a crucial mediator of MASH and clarify a new metabolic signaling axis between the hepatocytes and macrophages, implying that GCA can emerge as a particularly interesting putative therapeutic target for reversing MASH progression.

Abstract The colloidal gold nanoparticle (AuNP)‐based colorimetric lateral flow assay (LFA) is one of the most promising analytical tools for point‐of‐care disease diagnosis. However, the low sensitivity and insufficient accuracy still limit its clinical application. In this work, a machine learning (ML)‐optimized colorimetric LFA with ultrasound enrichment is developed to achieve the sensitive and accurate detection of tau proteins for early screening of Alzheimer's disease (AD). The LFA device is integrated with a portable ultrasonic actuator to rapidly enrich microparticles using ultrasound, which is essential for sample pre‐enrichment to improve the sensitivity, followed by ML algorithms to classify and predict the enhanced colorimetric signals. The results of the undiluted serum sample testing show that the protocol enables efficient classification and accurate quantification of the AD biomarker tau protein concentration with an average classification accuracy of 98.11% and an average prediction accuracy of 99.99%, achieving a limit of detection (LOD) as sensitive as 10.30 pg mL−1. Further point‐of‐care testing (POCT) of human plasma samples demonstrates the potential use of LFA in clinical trials. Such a reliable lateral flow immunosensor with high precision and superb sensing performance is expected to put LFA in perspective as an AD clinical diagnostic platform.

Hepatocellular carcinoma (HCC) ranks as the fourth most common cause of mortality globally among all cancer types. Programmed cell death (PCD) is a crucial biological mechanism governing cancer progression, tumor expansion, and metastatic dissemination. Furthermore, the tumor microenvironment (TME) is critical in influencing overall survival (OS) and immune responses to immunotherapeutic interventions. From a multi-omics perspective, the combination of PCD and TME could help to predict the survival of HCC patient survival and immunotherapy response. Our study analyzed variations in the PCD- and TME-classifier used in the classification of HCC patients into two subgroups: PCD high-TME low and PCD low-TME high. In the following step, we compared the tumor somatic mutation (TMB), immunotherapy response, and functional annotation of both groups of patients. Lastly, Western Blot (WB) were conducted. The immunohistochemistry (IHC) was performed on the Human Protein Atlas (HPA). In the PCD–TME classifier, 23 PCD-related genes and three immune cell types were identified. Patients’ prognoses and responses to therapy could be accurately predicted using this model. The findings of this study provide a new instrument for the clinical management of HCC patients, and they contribute to the development of accurate treatment strategies for these patients.

IntroductionThe plant genome encodes a plethora of proteins with structural similarity to animal receptor protein kinases, collectively known as receptor-like protein kinases (RLKs), which predominantly localize to the plasma membrane where they activate their kinase domains to convey extracellular signals to the interior of the cell, playing crucial roles in various signaling pathways. Despite the large number of members within the RLK family, to date, only a few have been identified as pattern-recognition receptors (PRRs), leaving many potential RLKs that could play roles in plant immunity undiscovered.MethodsIn this study, a recombinant strategy was initially employed to screen the kinase domains of 133 RLKs in the Arabidopsis genome to determine their involvement in the pathogen-triggered immunity (PTI) pathway. Subsequently, 6 potential immune-related recombinant RLKs (rRLKs) were selected for the creation of transgenic materials and underwent functional characterization analysis. Finally, a sequence analysis was conducted on the kinase domains of these 133 RLKs as well as the known immune RLK receptor kinase domains from other species.ResultsIt was found that 24 rRLKs activated the PTI response in Arabidopsis fls2 mutant protoplasts following flg22 treatment. Consistently, when 6 of these rRLKs were individually expressed in fls2 background, they exhibited diverse PTI signal transduction capabilities via different pathways while all retained membrane localization. Intriguingly, sequence analysis revealed multiple conserved amino acid sites within kinase domains of these experimentally identified immune-related RLKs in Arabidopsis. Importantly, these patterns are also preserved in RLKs involved in PTI in other species.DiscussionThis study, on one hand, identifies common features that theoretically can enhance our understanding of immune-related RLKs and facilitate the discovery of novel immune-related RLKs in the future. On the other hand, it provides experimental evidence for the use of recombinant technique to develop diverse rRLKs for molecular breeding, thereby conferring high resistance to plants without compromising their normal growth and development.