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Abstract Understanding Pd effects on NOx storage and release is crucial for designing passive NOx adsorber (PNA) to control NOx emissions during diesel cold-starts. Herein, we report two oxidation states of Pd species on CexZr1-xO2 regulated by metal-support interaction. Pdδ+ (0

Abstract Objective Lung cancer, along with various other cancers, is characterized by increased glucose metabolism. The maximum standardized uptake value (SUVmax), derived from positron emission tomography-computed tomography (PET-CT), serves as an indicator of glucose metabolic activity in tumor lesions. This study aimed to evaluate the correlation between body mass index (BMI) and SUVmax in individuals with lung cancer. Methods This study included 41 patients with lung cancer, who were divided into two groups: Group 1 (n = 21), with a BMI greater than 22.4, and Group 2 (n = 20), with a BMI less than 22.4. All participants underwent 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging. The SUVmax was calculated by manually delineating the regions of interest. A t-test was performed to assess whether the differences in SUVmax between the two groups were statistically significant. Results The mean SUVmax for Group 1 was 11.20 ± 5.45, while for Group 2 it was 10.65 ± 5.96. Although the mean SUVmax was higher in Group 1 compared to Group 2, the difference between the groups was not statistically significant (P = 0.757). Conclusion The findings indicate a non-significant difference in glucose metabolism in lung cancer lesions between patients with different BMI levels. These results offer valuable insights into the metabolic characteristics of lung cancer and contribute to a deeper understanding of its pathophysiology.

Abstract Developing high-performance nanomedicines to enhance antitumor efficacy remains a hot point in the field of biomedicine. In this study, we designed a versatile nanocomposite (FeS₂@COF-HA/AIPH) integrating covalent organic frameworks (COF) functionalized with pyrite (FeS₂) for synergistic photothermal (PTT), chemodynamic (CDT), thermodynamic (TDT) therapies, and immunotherapy. The superior photothermal effects and catalytic capabilities of FeS₂@COF enabled a minimally invasive PTT/CDT combination. The nanoplatform, with its mesoporous structure, also served as a drug delivery system, encapsulating the thermos-decomposable initiator AIPH. The hyaluronic acid (HA) coating not only improved tumor-targeting efficiency but also prevented nonspecific AIPH release. Under near-infrared (NIR) irradiation, the localized hyperthermia triggered AIPH decomposition, generating toxic alkyl radicals (•R) for TDT, further enhancing CDT efficiency. The combination of PTT, CDT, TDT, and immunotherapy led to potent antitumor effects with minimal systemic toxicity, both in vitro and in vivo. Notably, the nanoplatform effectively reprogrammed tumor-associated macrophages (TAMs) from an M2 to M1 phenotype, boosting antitumor immunity. This multifunctional platform thus offers a promising strategy for integrated PTT, CDT, TDT, and immune activation in tumor therapy.

Abstract Background This study aims to analyse the clinical characteristics of different types of odontogenic jawbone cysts (OJCs) and to provide a theoretical basis for prevention and clinical treatment. Methods Data from 1,038 patients with OJCs were collected, and relevant information, such as sex, age, clinical symptoms and signs, imaging data, number of lesions, lesion location, pathological diagnosis, clinical treatment and prognosis, was statistically analysed. Results According to the World Health Organization (WHO) classification of OJCs in 2022, the highest incidence rate was observed for radicular cysts (RCs), accounting for 58.96% of the total number of cases, followed by dentigerous cysts (DCs), accounting for approximately 23.22% of cases. lateral periodontal cysts (LPCs) and calcifying odontogenic cysts (COCs) comprised the lowest number of cases. The age distribution of patients was between 4 and 89 years, and the high incidence age group was youth and middle age, accounting for 66.67% of the total number of cases. The male-to-female ratio of patients was 1.51:1, and there was a statistically significant difference between the sexes(p

Abstract Background Overcoming resistance to Osimertinib in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) is clinically challenging because the underlying mechanisms are not fully understood. The murine double minute 2 (MDM2) has been extensively described as a tumor promotor in various malignancies, mainly through a negative regulatory machinery on the p53 tumor suppressor. However, the significance of MDM2 on the sensitivity to Osimertinib has not been described. Methods Osimertinib resistant cells were generated by standard dose escalation strategy and individual resistant clones were isolated for MDM2 testing. The MDM2 and its mutant constructs (ΔPBD, ΔRING, C464A) were introduced into PC-9, HCC827 and H1975 cells and evaluated for the sensitivity to Osimertinib by MTT assay, colony formation, EdU assay and TUNEL assay. MDM2 expression in resistant cells was manipulated by pharmacological and molecular approaches, respectively. Proteins that were implicated in PI3K/Akt, MAPK/Erk and apoptosis signaling were measured by Western blot analysis. Candidate proteins that interacted with MDM2 were captured by immunoprecipitation and probed with indicated antibodies. Results In comparison with parental PC-9 cells, the PC-9 OR resistant cells expressed high level of MDM2. Ectopic expression of MDM2 in PC-9, HCC827 and H1975 sensitive cells generated an Osimertinib resistant phenotype, regardless of p53 status. MDM2 promoted resistance to Osimertinib through a PI3K/Akt and MAPK/Erk-independent machinery, in contrast, MDM2 selectively stabilized MCL-1 protein to arrest Osimertinib-induced cancer cell apoptosis. Mechanistically, MDM2 acted as a E3 ligase to ubiquitinate FBW7, a well-established E3 ligase for MCL-1, at Lys412 residue, which resulted in FBW7 destruction and MCL-1 stabilization. Targeting MDM2 to augment MCL-1 protein breakdown overcame resistance to Osimertinib in vitro and in vivo. Finally, the clinical relevance of MDM2-FBW7-MCL-1 regulatory axis was validated in mouse xenograft tumor model and in NSCLC specimen. Conclusion Overexpression of MDM2 is a novel resistant mechanism to Osimertinib in EGFR mutant NSCLC. MDM2 utilizes its E3 ligase activity to provoke FBW7 destruction and sequentially leads to MCL-1 stabilization. Cancer cells with aberrant MDM2 state are refractory to apoptosis induction and elicit a resistant phenotype to Osimertinib. Therefore, targeting MDM2 would be a feasible approach to overcome resistance to Osimertinib in EGFR mutant NSCLC.

Abstract Qingdai (QD), derived from various plant sources, is commonly used in traditional Chinese medicine for ulcerative colitis (UC) treatment. However, the clinical efficacy and mechanisms of orally administered QD remain unclear. This study aims to evaluate QD’s efficacy in UC treatment and uncover its active components and mechanisms. A randomized controlled trial compared QD to Adisa, followed by UPLC-Q-TOF/MS and network pharmacology analyses to identify QD’s core components and targets. In vivo experiments on a UC mouse model explored QD’s impact on the AHR-Th17/Treg pathway using PCR, WB, ELISA, and flow cytometry. Results showed QD’s efficacy in UC treatment, with mucosal healing and remission comparable to Adisa. UPLC-Q-TOF/MS identified 16 core components in mouse colon tissue, with network pharmacology revealing 67 targets, potentially involving the IL-17 signaling pathway and Th17 cell differentiation. QD and its components up-regulated AHR, CYP1A1, and Foxp3, while down-regulating RORγt. Additionally, QD modulated pro-inflammatory (IL-6, IL-17 A) and anti-inflammatory (IL-10, TGF-β1) factors, and Treg/Th17 cell ratios in LPMC. Oral QD administration effectively promoted mucosal healing and improved UC symptoms, potentially through AHR-Th17/Treg pathway regulation.

Abstract The digital twin model of mine ventilation system (DTMVS) plays an important role in intelligent safety management. However, the uncertainty of the ventilation resistance coefficient, which is the core parameter of the model, makes it challenging to accurately construct a DTMVS. In this study, Latin Hypercube Sampling (LHS) and ventilation resistance coefficient estimation models (VRCEMs) are used to analyze the uncertainty. First, the LHS method was used to explore the effect of uncertainty in the simulated airflow by continuously increasing the level of uncertainty in the ventilation resistance coefficients. Subsequently, the ventilation resistance coefficients were estimated using the VRCEMs, and the uncertainty of the ventilation resistance coefficient and the simulated airflow was analyzed. The results showed that the ventilation resistance coefficients with a 5% coefficient of variation can cause the DTMVS to lose 34% of the real airflow data points. The degree of uncertainty in the ventilation resistance coefficients estimated by the VRCEM-GA (VRCEM using genetic algorithm) and VRCEM-DE (VRCEM using differential evolution algorithm) methods was enhanced by 27.4% and 4.4%, respectively, compared with VRCEM-ES (VRCEM using evolutionary strategy algorithm). The VRCEM-ES model had the least influence on the uncertainty of the simulated airflow of DTMVS. The simulated airflow of the DTMVS constructed based on VRCEMs fluctuated normally within the confidence interval. VRCEMs had a higher sensitivity to the ventilation resistance coefficients of branches with low coefficients of variation.

Abstract This was a multicenter, single-arm, open-label, phase Ib/II study (NCT04255576), aimed to evaluate the efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone (GCTB). JMT103 (2 mg/kg) was administered subcutaneously every four weeks, with loading doses on days 8 and 15. The primary endpoint was the objective tumor response rate (OTR) based on best response, defined as the proportion of patients who achieved elimination of at least 90% of the giant cells or radiologic complete or partial response per the modified Inverse Choi density/size (mICDS) or modified European Organization for Research and Treatment of Cancer (mEORTC) within 12 weeks. Secondary endpoints included objective response rate (ORR) per mICDS and mEORTC, and safety. A total of 139 patients were enrolled, and 135 were analyzed for efficacy. OTR, determined by the independent review committee (IRC) was 93.3% (95% CI 87.7-96.9). Treatment-related adverse events occurred in 90 (64.7%) patients, with hypophosphatemia and hypocalcemia being the most common. No serious treatment-related adverse events were observed. Thus, JMT103 demonstrates potential as a therapeutic option for GCTB.

Abstract Background Stress urinary incontinence (SUI), a common disorder of the pelvic floor, often results in anxiety, poor quality of life, and psychological issues among its sufferers. The relationship between lipid accumulation products (LAP) and stress-related urine incontinence remains unclear. This research aimed to investigate any possible correlation between the risk of SUI and the level of lipid accumulation products. Methods For this cross-sectional research, people with SUI who were 20 years of age or older were recruited using information from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. A weighted multivariate logistic regression model was used to evaluate the findings. As a potential biomarker, lipid accumulation product levels were sorted among individuals in ascending order and subjected to a trend test (P for trend). Additionally, a nonlinear analysis was conducted using smooth curve-fitting methods. Lipid accumulation products' effectiveness in predicting SUI was evaluated using receiver operating characteristic (ROC) curves. Finally, a subgroup analysis was performed to confirm that the connection between SUI and lipid accumulation products was consistent across all demographic groups. Results A thorough survey performed on 14,945 participants indicated that 23.61% of the respondents had SUI. A noteworthy association was observed between higher lipid accumulation product values and a greater probability of SUI in multivariate logistic regression analysis. Specifically, the stratification of lipid accumulation products into quartiles demonstrated a substantial positive correlation between the upper and lower quartiles, as evidenced by an elevated odds ratio for SUI (OR = 1.92; 95%CI 1.51–2.44; P

Abstract In this paper, we explore the quantum properties of three-flavor neutrino propagating in a Schwarzschild metric. It is found that the different strength of gravitational effects are obtained by adjusting the magnitude of $$\mathrm GM$$ G M arising in the oscillation phase. Using the weak field approximations, we show that the gravitational effects can make the entanglement oscillates over a large rage when $$\textrm{GM}=5.1\times 10^8 \, \textrm{Km}$$ GM = 5.1 × 10 8 Km and $$\textrm{GM}=7\times 10^7 \, \textrm{Km}$$ GM = 7 × 10 7 Km , respectively, Moreover, for $$\textrm{GM}=4.8\times 10^8 \, \textrm{Km}$$ GM = 4.8 × 10 8 Km and $$\textrm{GM}=9.3\times 10^7 \, \textrm{Km}$$ GM = 9.3 × 10 7 Km , the suppression of the entanglement can be observed due to the gravitational effects. Meanwhile, in this case, the gravitational effects also make the distribution of entanglement tighter through investing the entanglement complete monogamy relation. Furthermore, we examine the gravitational effects on the violation of the Svetlichny inequality to study the nonlocality of the system. It is shown that when $$\textrm{GM}=6\times 10^8 \, \textrm{Km}$$ GM = 6 × 10 8 Km and $$\textrm{GM}=7\times 10^7 \, \textrm{Km}$$ GM = 7 × 10 7 Km , the gravitational effects make the Svetlichny parameters always greater than 4, implying that the genuine tripartite nonlocality of the system is always present. However, the gravitational effects also restrain the violation of the Svetlichny to make the regions of the absence of nonlocality increase. The gravitational effects on the monogamy property of nonlocality lies in the change of the effective bound of the maximum bipartite nonlocality of the neutrinos system. Therefore, our investigations may be helpful to understanding of quantumness of the neutrinos system in curved space-time.

Abstract Background Buffalo is a globally important livestock species, but its reproductive performance is relatively low than cattles. At present, dominant follicle development specific process and mechanistic role of follicular growth related genes in water buffaloes are not well understood. Therefore, we comprehensively performed transcriptomics of granulosa cells and oocytes from different-sized follicles in water buffalo to identify key candidate genes that influence follicle development and diameter, and further explored the potential regulatory mechanisms of granulosa cells and oocytes in the process of water buffalo follicle development. Results In this study, we found918 granulosa cell transcripts and 1401 oocyte transcripts were correlated in follicles of different diameters, and the expression differences were significant. Subsequent enrichment analysis of the co-expressed differentially expressed transcripts identified several genes targeted by long non-coding RNAs (lncRNAs) and associated with follicular development. Notably, the upregulation of BUB1 regulated by MSTRG.41325.4 and interactive action of SMAD2 and SMAD7 might have key regulatory role in follicular development. Additionally, we also detected key differentially expressed genes that potentially influence follicular hormone metabolism and growth, like ID2, CHRD, TGIF2 and MAD2L1, and constructed an interaction network between lncRNA transcripts and mRNAs. Conclusions In summary, this study preliminarily revealed the differences in gene expression patterns among buffalo follicles of different sizes and their potential molecular regulatory mechanisms. It provides a new perspective for exploring the mechanism of buffalo follicular dominance and improving buffalo reproductive performance.

Abstract The mine wind speed sensor is an important intelligent sensing equipment in the mine intelligent ventilation system that can provide accurate and key wind speed parameters for the intelligent ventilation system. The turbulent pulsation characteristics of the airflow in the underground tunnel are a major factor for the inaccurate measurement of mine wind speed. Therefore, according to the random non-stationary characteristics of a turbulent pulsation signal, a denoising method based on adaptive complete ensemble empirical mode decomposition (CEEMDAN) combined with the wavelet threshold is proposed for suppressing the turbulent pulsation noise in the wind speed signal. First, the CEEMDAN algorithm is used for decomposing the wind speed signal into a series of IMF components. Second, the continuous mean square error criterion is used for determining the high-frequency IMF components with more noise. The wavelet threshold denoising method is used for denoising the high-frequency IMF components with more noise. Finally, the denoised IMF components and remaining low-frequency IMF components are reconstructed for obtaining the denoised signal. The results of the denoising analysis of measured turbulent pulsation signals, comparative analysis of denoising of simulated turbulent pulsation signals by different joint denoising methods, and denoising analysis of actual mine wind speed sensor data indicate that the joint denoising method proposed in this study has a higher signal-to-noise ratio and lower root mean square error of the wind speed signal after denoising. Compared with the EMD-wavelet threshold and EEMD-wavelet threshold denoising methods, the denoising method proposed in this study is better and has higher denoising accuracy, which provides a new method for processing actual mine wind speed sensor data.

Abstract MRI (magnetic resonance imaging) images can effectively show the placental haemorrhage area. In view of the special properties and real‐time detection requirements of placental haemorrhage MRI images, this paper has systematically improved the single‐shot multi‐box detector (SSD) target detection algorithm (M‐SSD). First, taking advantage of the particularity of the MRI image, the maximum stable extremum region (MSER) algorithm was used as the anchor proposal network which integrated the proposal information into the feature layer of SSD to avoid the hungry traversal of the original algorithm. Second, after the scale statistics of the placental haemorrhage area in MRI images, the bounding box matching the size of the placental haemorrhage area was redefined, in this way, the scale of the bounding box will have application pertinence, which can effectively improve the detection accuracy of the algorithm. Third, due to the small target property of the placental haemorrhage area in the MRI image, the VGG16 basic network in the original SSD was replaced by ResNet101, this made the algorithm have higher performance in small target detection. Finally, the Placental Haemorrhage MRI Detection Database (PHMD) has been built which is not only a base for this paper, but also for further research in this area.

Abstract Background Hepatic venous pressure gradient (HVPG) is considered the gold standard for diagnosing portal hypertension (PHT). Laparoscopic splenectomy plus esophagogastric devascularization (LSED) is an important surgery for treating PHT. However, the variation trend of HVPG after surgery is not clear. Moreover, whether HVPG can provide precise prognostic information for patients undergoing surgery remains to be further studied. This study aimed to investigate the independent prognostic value of HVPG in LSED. Methods From January 2016 to March 2023, 135 patients with PHT underwent LSED at our hospital were retrospectively evaluated. We analyzed the correlations between clinical indicators and history of upper gastrointestinal bleeding (UGIB). Among them, 57 patients remeasured postoperative HVPG. We further investigated the postoperative alterations of HVPG and correlative factors, as well as the relationship between the HVPG and postoperative UGIB. Results In this study, we found that 94 patients with preoperative UGIB (16.27 ± 5.73 mmHg) had a higher baseline HVPG than the other 41 patients without (14.02 ± 5.90 mmHg) (p = 0.04). The mean postoperative HVPG significantly decreased (-3.57 ± 8.09 mmHg, p = 0.001) compared to the baseline, and 66% of patients (38/57) experienced a decreased HVPG-response after surgery. The baseline HVPG and preoperative CTP class B were associated with the decreased HVPG-response (p20% from baseline exhibited better recurrent hemorrhage-free survival rates than those without (log-rank, p = 0.013). Conclusion We found that LSED led to a significantly decreased HVPG, and patients with postoperative HVPG decreased >20% obtained better UGIB-free survival benefits than those without.

Granitic veins (GVs) have a significant influence on the mechanical responses of tunnels excavated in granitic strata. Distinguishing the mechanical properties of host granites (HGs), GVs and vein-granite interfaces (VGIs) is critical. For this, this paper analyzed the mechanical behaviors and rupture processes of typical HG, GV, and VGI samples under uniaxial compression condition. For the rocks studied, although the linear axial stress‒strain relation can be identified and the deformation modulus can be determined, the transverse deformation developed nonlinearly with axial stress. As a result, the instantaneous Poisson's ratio increases continuously and may even exceed 0.5, making it extremely difficult to accurately determine the Poisson's ratio. In addition, the studied GV samples were found to be significantly brittle, indicating that large-scale GVs cannot be ignored when assessing rockburst hazards in granitic strata with brittle GVs. In terms of the rupture process, the HG and GV samples were gradually damaged by the formation of small-scale cracks and then ruptured by large cracks formed from small-scale cracks, whereas the VGI samples ruptured along large cracks with significant energy release. By examining the characteristic stress thresholds of these three granites, it is noted that the crack closure stress σcc exceeds both the crack initiation stress σci and the crack damage stress σcd for the HG and VGI samples. The transverse damage to a tested sample appears to be significantly greater than the axial damage, which is essentially related to the rock grain size and grain size distribution.

Abstract In this work, we investigate short-packet communications in power beacon (PB)-assisted Internet-of-Things (IoT) networks, where an energy-constrained actuator first harvests energy from a dedicated PB, and then transmits confidential signals to a desired controller in the presence of an eavesdropper. We derive a closed-form lower bound approximation expression for the average achievable effective secrecy rate (AESR) over Nakagami-m fading channels. To gain more insights, we also present the asymptotic average AESR in the high signal-to-noise ratio (SNR) regime. Specifically, analytical results indicate that an average AESR floor appears with the increase of SNR. Moreover, a low complexity one-dimensional search method is employed to maximize the average AESR by optimizing the energy harvesting length. Monte-Carlo simulations are provided to corroborate our analysis.

Abstract The Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2) has great potential for development due to its advantages of the use of multiple beams, low energy consumption, high repetition frequency, and high measurement sensitivity. However, the weak photon signal emitted by the photon counting lidar is susceptible to the background noise caused by the sun and the atmosphere, which can seriously affect the processing and application of laser data. This paper proposes an improved DBSCAN clustering algorithm for denoising single photon laser point clouds in mountainous areas. Firstly, a grouping method based on elevation and distance statistics is proposed to reduce the influence of terrain undulations on denoising accuracy. Finally, an automatic radius search method is put forward to determine clustering radius of each group, automatically find the optimal radius, and improve the existing DBSCAN clustering method. The method proposed in this paper is compared with the classical DBSCAN algorithm. The results show that the proposed algorithm significantly improves denoising accuracy in mountainous areas and effectively filters out most background noise. Graphical Abstract

Abstract Background Cold is an important environmental limiting factor affecting plant yield and quality. Capsicum (chili pepper), a tropical and subtropical vegetable crop, is extremely sensitive to cold. Although H2S is an important signaling regulator in the responses of plant growth and development to abiotic stress, few studies have examined its effects on cold-sensitive capsicum varieties. Through biotechnology methods to enhance the cold resistance of peppers, to provide some reference for pepper breeding, investigated molecular regulation by H2S of responses to cold stress in cold-sensitive capsicum plants, via physiological and transcriptomic analyses. Results In capsicum seedlings, exogenous H2S enhanced relative electrical conductivity (REC) and levels of malondialdehyde (MDA) under cold stress, maintained membrane integrity, increased the activity of enzymatic and non-enzymatic antioxidants, balanced reactive oxygen species levels (O2 ·− and H2O2), and improved photosynthesis, mitigating the damage caused by cold. In addition, 416 differentially expressed genes (DEGs) were involved in the response to cold stress after H2S treatment. These DEGs were mainly enriched in the ascorbate–glutathione and starch–sucrose metabolic pathways and plant hormone signal-transduction pathways. Exogenous H2S altered the expression of key enzyme-encoding genes such as GST, APX, and MDHAR in the ascorbate–glutathione metabolism pathway, as well as that of regulatory genes for stimulatory hormones (auxin, cytokinins, and gibberellins) and inhibitory hormones (including jasmonate and salicylic acid) in the plant hormone signal-transduction pathway, helping to maintain the energy supply and intracellular metabolic stability under cold stress. Conclusions These findings reveal that exogenous H2S improves cold tolerance in cold-sensitive capsicum plants, elucidating the molecular mechanisms underlying its responses to cold stress. This study provides a theoretical basis for exploring and improving cold tolerance in capsicum plants.

Abstract Background Aldo-keto reductase family 1 member C3 (AKR1C3) is a radioresistance gene in esophageal cancer. This study aimed to investigate the signaling pathways that mediate the regulatory role of AKR1C3 in the radioresistance of esophageal cancer cells. Methods The protein levels of AKR1C3 in cancer tissue samples were compared between patients with radiosensitive and radioresistant esophageal cancer using immunohistochemical staining. AKR1C3-silenced stable KYSE170R esophageal cancer cells (KY170R-shAKR1C3) were established. Colony formation assay was employed to evaluate the radiosensitivity of cancer cells, while flow cytometry analysis was utilized to quantify reactive oxygen species (ROS) production in these cells. Additionally, Western blotting was conducted to determine protein expression levels. Results AKR1C3 protein exhibited significantly higher expression in radioresistant cancer tissue samples compared to radiosensitive samples. AKR1C3 silencing promoted radiosensitivity and ROS production of KYSE170R cells. At 32 h after X-ray radiation, the levels of total and phosphorylated ERK1/2, JNK, and AKT proteins were significantly elevated in KYSE170R-shAKR1C3 cells compared to untransfected KYSE170R cells. The inhibitor of AKR1C3 remarkably enhanced the radiosensitivity of KYSE170R cells. Conversely, treatment with either a MEK inhibitor or an AKT inhibitor significantly increased the radioresistance of KYSE170R-shAKR1C3 cells. Conclusions Our results suggest that AKR1C3 mediates radioresistance of KYSE170R cells possibly through MAPK and AKT signaling.

Abstract The Nipah virus (NiV), a member of the Paramyxoviridae family, is notorious for its high fatality rate in humans. The RNA polymerase machinery of NiV, comprising the large protein L and the phosphoprotein P, is essential for viral replication. This study presents the 2.9-Å cryo-electron microscopy structure of the NiV L-P complex, shedding light on its assembly and functionality. The structure not only demonstrates the molecular details of the conserved N-terminal domain, RNA-dependent RNA polymerase (RdRp), and GDP polyribonucleotidyltransferase of the L protein, but also the intact central oligomerization domain and the C-terminal X domain of the P protein. The P protein interacts extensively with the L protein, forming an antiparallel β-sheet among the P protomers and with the fingers subdomain of RdRp. The flexible linker domain of one P promoter extends its contact with the fingers subdomain to reach near the nascent RNA exit, highlighting the distinct characteristic of the NiV L-P interface. This distinctive tetrameric organization of the P protein and its interaction with the L protein provide crucial molecular insights into the replication and transcription mechanisms of NiV polymerase, ultimately contributing to the development of effective treatments and preventive measures against this Paramyxoviridae family deadly pathogen.

Abstract Chronic active Epstein-Barr virus infection (CAEBV) is a progressive and life-threatening disease characterized by persistent or recurrent EBV activation. It has been reported that, γδ T cells, a type of cytotoxic lymphocyte, play a critical role in restricting EBV. However, the functional status of γδ T cells in pediatric CAEBV patients has not yet been described. In this study, flow cytometry analysis was conducted to explore the cytokine production capacity of γδ T cells in CAEBV patients. A diminished frequency of γδ T cells and decreased expression of cytolytic molecule granzyme B were found in CAEBV patients, suggesting a dysfunction in the immune regulatory function of γδ T cells in this disease.

Abstract Value co-creation can be defined as the joint benefit that is created by patients and medical service providers through the integration of their respective resources. Participation and interaction between doctors and patients can generate an outcome that benefits both sides. Relevant studies of value co-creation in the healthcare field are limited. This study established hypotheses to explore the association between doctor interaction behavior, patient participation in value co-creation, and patient satisfaction. A cross-sectional survey was conducted with 637 patients (outpatients and inpatients) at a tertiary-level hospital in Guangzhou, China. The analysis result indicated that doctor interaction behavior could stimulate patient participation in value co-creation then increase patient satisfaction. The standardized total effect, direct effect, and indirect effect were 0.641 (95%CI: 0.055 ~ 0.067), 0.546 (95%CI: 0.044 ~ 0.059), and 0.095 (95%CI: 0.032 ~ 0.166), respectively. Patient participation in value co-creation mediated the relationship between doctor interaction behavior and patient satisfaction. Among the different dimensions of doctor interaction behavior, access, risk assessment and transparency dimensions were associated with positive patient participation in value co-creation. During the treatment process, doctor interaction and patient participation can get satisfying results.

Abstract Purpose DNA methylation prominently inactivates tumor suppressor genes and facilitates oncogenesis. Previously, we delineated a chromosome 18 deletion encompassing the erythrocyte membrane protein band 4.1-like 3 (EPB41L3) gene, a progenitor for the tumor suppressor that is differentially expressed in adenocarcinoma of the lung-1 (DAL-1) in gastric cancer (GC). Methods Our current investigation aimed to elucidate EPB41L3 expression and methylation in GC, identify regulatory transcription factors, and identify affected downstream pathways. Immunohistochemistry demonstrated that DAL-1 expression is markedly reduced in GC tissues, with its downregulation serving as an independent prognostic marker. Results High-throughput bisulfite sequencing of 70 GC patient tissue pairs revealed that higher methylation of non-CpGs in the EPB41L3 promoter was correlated with more malignant tumor progression and higher-grade tissue classification. Such hypermethylation was shown to diminish DAL-1 expression, thus contributing to the malignancy of GC phenotypes. The DNA methyltransferase inhibitor 5-aza-2’-deoxycytidine (5-aza-CdR) was found to partially restore DAL-1 expression. Moreover, direct binding of the transcription factor CDC5L to the upstream region of the EPB41L3 promoter was identified via chromosome immunoprecipitation (ChIP)-qPCR and luciferase reporter assays. Immunohistochemistry confirmed the positive correlation between CDC5L and DAL-1 protein levels. Subsequent RNA-seq analysis revealed that DAL-1 significantly influences the extracellular matrix and space-related pathways. GC cell RNA-seq post-5-Aza-CdR treatment and single-cell RNA-seq data of GC tissues confirmed the upregulation of AREG and COL17A1, pivotal tumor suppressors, in response to EPB41L3 demethylation or overexpression in GC epithelial cells. Conclusion In conclusion, this study elucidates the association between non-CpG methylation of EPB41L3 and GC progression and identifies the key transcription factors and downstream molecules involved. These findings enhance our understanding of the role of EPB41L3 in gastric cancer and provide a solid theoretical foundation for future research and potential clinical applications.

In individuals afflicted with hemophilia, characterized by a deficiency of coagulation factor VIII (FVIII), the occurrence of spontaneous recurrent intra-articular hemorrhage precipitates the emergence of hemophilic arthropathy (HA). Although clotting factor replacement therapy reduces joint bleeding clinically, clotting factors need to be injected frequently due to the rapid diffusion of the drug. Hence, a novel drug delivery approach may be developed to improve the drug therapy. Platelet-derived extracellular vesicles (PEVs) are known to possess anti-inflammatory and hemostatic properties and could be used as a potential HA therapy. In this study, we constructed a PEV-LS@FVIII nanotherapeutic system by combining thioketal (TK), liposomes (LS), and FVIII to form the LS@FVIII complexes, and then hybridizing PEV with LS@FVIII. Our results demonstrated that PEV-LS@FVIII could efficiently facilitate FVIII delivery and specifically target the injured knee joint. Both in vitro and in vivo studies showed a reduction in the M1 phenotype of macrophages and an enhancement of the M2 phenotype, compared to FVIII free control. Furthermore, PEV-LS@FVIII appeared to alleviate HA-induced cartilage damage. In conclusion, our findings demonstrate that PEV-LS@FVIII could delay the progression of HA by targeting bleeding joints, modulating macrophage polarization to suppress inflammation, and mitigating cartilage damage.

Objective At present, due to the lack of early observation methods, the effect of the ‘accordion’ technique on the treatment of nonunion of the docking site varies greatly. In this study, color Doppler ultrasound was used to observe the docking site's local changes and investigate the relationship between local microenvironment changes and bone healing after the accordion technique. Methods 30 patients with tibial bone transport treated at the Department of Orthopedics, Second Hospital of Shanxi Medical University, from May 2018 to June 2022, were analyzed retrospectively. Paired‐sample t‐tests were used for data that conformed to a normal distribution, and paired rank‐sum tests were used for before‐and‐after comparisons that did not conform to a normal distribution. There were 26 males and 4 females, aged 47.3 ± 11.7 years. Before bone transport, the defect gap between tibial bone ends was 6.80 ± 3.61 cm. The steps of the accordion technique were as follows: compression for 7 days, ultrasonic study of the microenvironment at the docking site, distraction for 12 days, latency for 7 days, compression for 14 days, then static fixation and radiological study until complete bone healing. Ultrasound was used to detect the size of the hematoma after 7 days of pressure, and the changes in blood flow before and after the ‘accordion' operation. Results All patients were followed up for 11.9 ± 1.9 months. At the last follow‐up, 22 patients achieved bone healing at the docking site after the treatment of the ‘accordion’ technique. There was a linear negative correlation between the size of the hematoma and the time of bone healing at the docking site (r = −0.639, p

Rechargeable magnesium-ion (Mg-ion) batteries have attracted wide attention for energy storage. However, magnesium anode is still limited by the irreversible Mg plating/stripping procedure. Herein, a well-designed binary Bi2O3-Bi2S3 (BO-BS) heterostructure is fulfilled by virtue of the cooperative interface and energy band engineering targeted fast Mg-ion storage. The built-in electronic field resulting from the asymmetrical electron distribution at the interface of electron-rich S center at Bi2S3 side and electron-poor O center at Bi2O3 side effectively accelerates the electrochemical reaction kinetics in the Mg-ion battery system. Moreover, the as-designed heterogenous interface also benefits to maintaining the electrode integrity. With these advantages, the BO-BS electrode displays a remarkable capacity of 150.36 mAh g−1 at 0.67 A g–1 and a superior cycling stability. This investigation would offer novel insights into the rational design of functional heterogenous electrode materials targeted the fast reaction kinetics for energy storage systems.

Abstract Black goats are a significant meat breed in southern China. To investigate the expression patterns and biological functions of genes in various tissues of black goats, we analyzed housekeeping genes (HKGs), tissue-specific genes (TSGs), and hub genes (HUBGs) across 23 tissues. Additionally, we analyzed HKGs in 13 tissues under different feeding conditions. We identified 2968 HKGs, including six important ones. Interestingly, HKGs in grazing black goats demonstrated higher and more stable expression levels. We discovered a total of 9912 TSGs, including 134 newly identified ones. The number of TSGs for mRNA and lncRNA were nearly equal, with 127 mRNA TSGs expressed solely in one tissue. Additionally, the predicted functions of tissue-specific long non-coding RNAs (lncRNAs) targeting mRNAs corresponded with the physiological functions of the tissues.Weighted gene co-expression network analysis (WGCNA) constructed 30 modules, where the dark grey module consists almost entirely of HKGs, and TSGs are located in modules most correlated with their respective tissues. Additionally, we identified 289 HUBGs, which are involved in regulating the physiological functions of their respective tissues. Overall, these identified HKGs, TSGs, and HUBGs provide a foundation for studying the molecular mechanisms affecting the genetic and biological processes of complex traits in black goats.

Abstract Determination of high sulfur content in sulfide minerals is crucial for various applications, including geochemistry, mining, and environmental monitoring. While inductively coupled plasma optical emission spectrometry (ICP-OES) is the preferred method for sulfur analysis, conventional sample preparation techniques often fall short when dealing with high sulfur concentrations. This study investigated optimized digestion conditions for accurate sulfur determination in sulfide minerals using ICP-OES. We employed anti-corrosion acid digestion bombs, an aqua regia–hydrofluoric acid system, and a digestion temperature of 180 °C, achieving exceptional results. Certified reference material recoveries ranged from 99.9 to 100.5%, with relative standard deviations between 0.42 and 0.84%. These results demonstrate the high accuracy and precision of the method. The optimized digestion protocol presented in this study provides a robust and reliable approach for accurate sulfur analysis in sulfide minerals, particularly for high concentrations.

Abstract Background Urinary incontinence (UI) is a prevalent, health-threatening condition that causes isolation and psychological strain, leading to significant personal distress. The connection between the triglyceride glucose body mass index (TyG-BMI) and UI remains elusive. The purpose of the current research was to investigate any possible relationships between raised TyG-BMI levels and a higher likelihood of UI. Methods For a thorough examination, adults 20 years and older with UI were included in cross-sectional research using the data obtained from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. Our investigation centred on three of the significant varieties of UI: Urgent Urinary Incontinence (UUI), Mixed Urinary Incontinence (MUI), and Stress Urinary Incontinence (SUI), employing weighted multivariate logistic regression models for an in-depth evaluation. The TyG-BMI, a possible biomarker, was arranged in increasing order among participants and then assessed with a trend test (P for trend). Moreover, this investigation delved into the non-linear relationships using advanced smoothed curve fitting techniques. Meticulous subgroup analyses were executed to verify the uniformity of the UI and TyG-BMI relationship across diverse demographic groups. Results A thorough investigation was conducted with 18,751 subjects to analyze the prevalence and types of UI, showing that 23.59% of individuals suffered from SUI, 19.42% from UUI, and 9.32% from MUI. Considering all possible confounding variables, Multivariate logistic regression analysis showed a substantial relationship between elevated TyG-BMI values and a greater likelihood across all UI categories. Specifically, stratifying the TyG-BMI into quartiles revealed a pronounced positive correlation in the top quartile relative to the bottom, reflected in increased odds ratios for SUI, UUI, and MUI (SUI: OR = 2.36, 95% CI 2.03–2.78, P

Abstract Liver metastasis of colorectal cancer (CRC) is a leading cause of death among cancer patients. The overexpression of glucose transporter 1 (Glut1) and enhanced glucose uptake that are associated with the Warburg effect are frequently observed in CRC liver metastases, but the underlying mechanisms remain poorly understood. CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6) regulates the intracellular trafficking of programmed death-ligand-1 (PD-L1); therefore, we investigated whether CMTM6 regulates Glut1 trafficking and the Warburg effect in CRC cells. We found that knocking down of CMTM6 by shRNA induced the lysosomal degradation of Glut1, decreased glucose uptake and glycolysis in CRC cells, and suppressed subcutaneous CRC growth in nude mice and liver metastasis in C57BL/6 mice. Mechanistically, CMTM6 forms a complex with Glut1 and Rab11 in the endosomes of CRC cells, and this complex is required for the Rab11-dependent transport of Glut1 to the plasma membrane and for the protection of Glut1 from lysosomal degradation. Multiomics revealed global transcriptomic changes in CMTM6-knockdown CRC cells that affected the transcriptomes of adjacent cancer-associated fibroblasts from CRC liver metastases. As a result of these transcriptomic changes, CMTM6-knockdown CRC cells exhibited a defect in the G2-to-M phase transition, reduced secretion of 60 cytokines/chemokines, and inability to recruit cancer-associated fibroblasts to support an immunosuppressive CRC liver metastasis microenvironment. Analysis of TCGA data confirmed that CMTM6 expression was increased in CRC patients and that elevated CMTM6 expression was associated with worse patient survival. Together, our data suggest that CMTM6 plays multiple roles in regulating the Warburg effect, transcriptome, and liver metastasis of CRC.

Ophiocordyceps encompasses over 300 species, demonstrating a wide range of morphological features, hosts and habitats within its species diversity. In this study, two novel species in Ophiocordyceps were revealed parasitising Hepialidae larva buried in soil. Ophiocordyceps albastroma was morphologically characterised by white stromata, solitary and cylindrical conidiogenous cells and smooth ovoid or ellipsoidal conidia. Ophiocordyceps nigristroma was characterised by woody and dark brown stromata, monophialidic, swollen base and lageniform conidiogenous cells and smooth fusiform or oval conidia. The two new species formed a separate clade, respectively, based on the phylogenetic analyses of a combined dataset including nrSSU, nrLSU, rpb1, rpb2, and tef-1α, as well as a dataset of mitochondrial 14 protein coding genes (PCGs). They were all closely grouped with O. sinensis. The mitochondrial genomes of them were first reported. Their mitogenomes were all typical of circular molecules, with positive AT and GC skew, similar GC content, similar genetic composition, similar codon usage and conservative gene positions. However, the length of the mitogenomes varied. Changes in the length of the genes were the leading cause of changes in the length of mitochondrial genome of Ophiocordyceps. The discovery and identification of new Ophiocordyceps species and analysis their mitochondrial genomes may serve as foundations for phylogeny and diversity research within the genus Ophiocordyceps.

Abstract Background The ANA-grade, encompassing early-diverging angiosperm lineages, Amborellales, Nymphaeales, and Austrobaileyales, represents a fundamental phase in the evolutionary history of flowering plants. Since the completion of key assembly of the Amborella genome, the continuous influx of omics data from the lineage underscores the need for a specialized database. Results Here, we introduce the ANA-grade Genome Database (ANAgdb, https://anagenome.cn/ ), which integrates multi-omics data including 11 genomes, 167 transcriptomes, and 10 miRNAomes, as well as extensive taxonomic details specific to the ANA-grade. Designed with an array of user-friendly tools, ANAgdb not only facilitates the effective storage, querying, and analysis of data but also enables the integration and dissemination of crucial genomic and taxonomic information. Conclusion By integrating the comprehensive resources and tools, ANAgdb aims to significantly advance research in phylogenomics and taxonomic studies, providing a robust platform for researchers to explore the genetic and morphological diversities of these ancient plant lineages.

Abstract LiDAR systems that rely on classical signals are susceptible to intercept-and-recent spoofing attacks, where a target attempts to avoid detection. To address this vulnerability, we propose a quantum-secured LiDAR protocol that utilizes Gaussian modulated coherent states for both range determination and spoofing attack detection. By leveraging the Gaussian nature of the signals, the LiDAR system can accurately determine the range of the target through cross-correlation analysis. Additionally, by estimating the excess noise of the LiDAR system, the spoofing attack performed by the target can be detected, as it can introduce additional noise to the signals. We have developed a model for target ranging and security check, and conducted numerical simulations to evaluate the Receiver Operating Characteristic (ROC) of the LiDAR system. The results indicate that an intercept-and-recent spoofing attack can be detected with a high probability at a low false-alarm rate. Furthermore, the proposed method can be implemented using currently available technology, highlighting its feasibility and practicality in real-world applications.

High-performance grinding wheels are critical tools for precision surface generation. In precision grinding processes, the coolant supply at the wheel-workpiece interface is critical for reducing grinding temperature and detrimental friction. For better lubrication and chip removal performance, the cavities or pores need to be generated throughout the grinding wheel. The ideal morphology of pores in grinding wheels should be inter-connected and capable of providing sufficient coolant. Conventional grinding wheel design and fabrication methods can only passively generate closed circular pores by using pore-forming agents. Increasing the percentage of pores in this way generally leads to an uncontrollable reduction in mechanical strength, while the closed pores are insufficient in cooling performance. In this paper, the grinding wheels with triply periodic minimal surface lattice structure are designed and fabricated, which achieves the regulable and inter-connected internal structure of grinding wheels. Meanwhile, to balance the relationship between the structural properties and performance indicators of porous grinding wheels, an optimal design method for the porous structure of grinding wheels is proposed. Finally, the grinding performance of the novel grinding wheels in comparison to electroplated diamond grinding wheels is investigated in terms of grinding force, specific grinding energy and ground surface roughness.

Abstract Background Intermediate cells are present in the early stages of human prostate development and adenocarcinoma. While primary cells isolated from benign human prostate tissues or tumors exhibit an intermediate phenotype in vitro, they cannot form tumors in vivo unless genetically modified. It is unclear about the stem cell properties and tumorigenicity of intermediate cells. Methods We developed a customized medium to culture primary human intermediate prostate cells, which were transplanted into male immunodeficient NCG mice to examine tumorigenicity in vivo. We treated the cells with different concentrations of dihydrotestosterone (DHT) and enzalutamide in vitro and surgically castrated the mice after cell transplantation in vivo. Immunostaining, qRT-PCR, RNA sequencing, and western blotting were performed to characterize the cells in tissues and 2D and 3D cultures. Results We found intermediate cells expressing AR+PSA+CK8+CK5+ in the luminal compartment of human prostate adenocarcinoma by immunostaining. We cultured the primary intermediate cells in vitro, which expressed luminal (AR+PSA+CK8+CK18+), basal (CK5+P63+), intermediate (IVL+), and stem cell (CK4+CK13+PSCA+SOX2+) markers. These cells resisted castration in vitro by upregulating the expression of AR, PSA, and proliferation markers KI67 and PCNA. The intermediate cells had high tumorigenicity in vivo, forming tumors in immunodeficient NCG mice in a month without any genetic modification or co-transplantation with embryonic urogenital sinus mesenchyme (UGSM) cells. We named these cells human castration-resistant intermediate prostate cancer stem cells or CriPCSCs and defined the xenograft model as patient primary cell-derived xenograft (PrDX). Human CriPCSCs resisted castration in vitro and in vivo by upregulating AR expression. Furthermore, human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in PrDX tumors in vivo, which can dedifferentiate into CriPCSCs in vitro. Conclusions Our study identified and established methods for culturing human CriPCSCs, which had high tumorigenicity in vivo without any genetic modification or UGSM co-transplantation. Human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in the fast-growing tumors in vivo, which hold the potential to dedifferentiate into intermediate stem cells. These cells resisted castration by upregulating AR expression. The human CriPCSC and PrDX methods hold significant potential for advancing prostate cancer research and precision medicine.

Abstract Extreme events with increasing frequency and intensity are significantly affecting the permafrost environment. Analysis using the ERA5-Land reanalysis data revealed that the permafrost region of the central Qinghai-Tibet Plateau (QTP) experienced the summer heat wave in 2022. Four active layer sites experienced maximum active layer thicknesses (ALT) in 2022 (mean: 207.7 cm), which was 20% higher than the mean ALT during 2000–2021 (mean: 175.9 cm). The mean annual ground temperature (MAGT) observed in 2022 was also the highest, exceeding the average of the previous years by 10%. The contribution fraction of heat wave to the seasonal thaw depth of active layer was quantified using Stefan model with ranging from 6.6% to 13.6%, and the maximum contribution fraction occurs in 2022. These findings are helpful to better understand the impact processes of extreme events on the active layer and permafrost.

Abstract Background The netrin-1/CD146 pathway regulates colorectal cancer (CRC) liver metastasis, angiogenesis, and vascular development. However, few investigations have yet examined the biological function of netrin-1/CD146 complex in CRC. In this work, we investigated the relationship between the netrin-1/CD146 axis and S100 proteins in sentinel lymph node, and revealed a possible new clue for vascular metastasis of CRC. Methods The expression levels of netrin-1 and CD146 proteins in CRC, as well as S100A8 and S100A9 proteins in the sentinel lymph nodes were determined by immunohistochemistry. Using GEPIA and UALCAN, we analyzed netrin-1 and CD146 gene expression in CRC, their association with CRC stage, and their expression levels and prognosis in CRC patients. Results The expression level of netrin-1 in N1a+1b (CRC lymphatic metastasis groups, exculded N1c) was positively increased with N0 (p = 0.012). The level of netrin-1 protein was positively correlated with CD146 protein (p 0.05). Conclusions The netrin-1/CD146 and netrin-1/S100A9 axis in CRC tissues might related with early stage of lymph node metastasis, thus providing potential novel channels for blocking lymphatic metastasis and guiding biomarker discovery in CRC patients.

Abstract Gastric cancer is one of the most malignant digestive tract tumors worldwide and its progression is associated with gene expression and metabolic alteration. We revealed that the gastric cancer patients with lower expression level of TOB1 exhibited poorer overall survivals according to the data in Kaplan–Meier Plotter. The unphosphorylated TOB1 protein which is effective expressed lower in gastric cancer cells. The gastric cancer cells with TOB1 gene depletion performed higher abilities of proliferation, migration and invasion and lower ability of apoptosis in vitro. The TOB1 gene depletion also promoted the tumorigenesis of gastric cancer cells in vivo. The gastric cancer cells with TOB1 gene overexpression had the converse behaviors. The transcriptional and metabolic sequencing was performed. The analyzation results showed that genes correlate-expressed with TOB1 gene were enriched in the pathways related to ERK pathway, including focal adhesion pathway, which was verified using real-time quantitative PCR. After inhibiting ERK pathway, the proliferation, colony formation and migration abilities were reduced in gastric cancer cells with low phosphorylated TOB1 protein expression level. Moreover, Pearson correlation analysis was adopted to further analyze the correlation of enriched metabolic products and differentially expressed genes. The expression of Choline, UDP-N-acetylglucosamine, Adenosine and GMP were related to the function of TOB1. This study demonstrates the genes and metabolites related to focal adhesion pathway and ERK pathway are the potential diagnosis and therapeutic targets to gastric cancer with TOB1 depletion.

We report unique two-step strain glass transition toward different local strain states in NiTi, i.e. R and B19′ strain glasses. This unique transition is evidenced by dynamic mechanical analysis and in-situ HR-TEM. A comprehensive phase diagram is established to illustrate diverse transition pathways and corresponding tunable superelastic properties. This pathway exploits the integrated transition of different phases, lowering the transition energy barrier, yielding superelasticity with large recoverable strain (6%), ultralow modulus (24 GPa) and robust cyclic and wide-temperature stability. Our investigation provides fresh insights into continuous transition pathways among different strain glass states to achieve exceptional properties in shape memory alloys.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

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.

TRIB3, a pseudokinase, was previously studied within only some specific cancer types, leaving its comprehensive functions in pan-cancer contexts largely unexplored. Here, we performed an integrated analysis of TRIB3 expression, prognosis, genetic alterations, functional enrichment and tumor immune-related characteristics in 33 cancer types. Our results showed that TRIB3 exhibits high expression levels across 24 different cancer types and correlates closely with unfavorable prognoses. Meanwhile, TRIB3 shows mutations in a wide spectrum of 22 distinct cancer types, with the predominant mutation types being missense mutations and gene amplifications, and significant changes in DNA methylation levels in 14 types of cancer. We further discovered that TRIB3 expression is significantly associated with cancer immune-related genome mutations, such as tumor mutational burden (TMB), microsatellite instability (MSI) and DNA mismatch repair (MMR), and infiltration of immunosuppressive cells, such as CD4+ Th2 cells and myeloid-derived suppressor cells (MDSCs), into the tumor microenvironment. These results indicated that the expression of TRIB3 might reshape the tumor immune microenvironment (TIME) and lead to immunosuppressive ''cold'' tumors. In addition, our results confirmed that the loss of function of TRIB3 inhibits cell proliferation, promotes apoptosis, and leads to significant enrichment of ''hot'' tumor-related immune pathways, at least in breast cancer cells, which further supports the important role of TRIB3 in cancer prognosis and TIME regulation. Together, this pan-cancer investigation provided a comprehensive understanding of the critical role of TRIB3 in human cancers, and suggested that TRIB3 might be a promising prognostic biomarker and a potential target for cancer immunotherapy.

Abstract The development of unstable carotid atherosclerotic plaques is associated with the induction of neutrophil extracellular traps (NETs) via the activation of diverse inflammatory mediators in the circulating bloodstream. However, the underlying mechanisms through which NETs influence the microenvironment of atherosclerotic plaques and contribute to the development of unstable carotid plaques remain largely elusive. The objective of this study was to elucidate the role of myeloid differentiation protein 1 (MD-1, LY86)-induced NETs underlying the crosstalk between unstable plaque formation and the plaque microenvironment. We employed bioinformatics analysis to identify key genes associated with carotid-unstable plaque, followed by comprehensive validation using various experimental approaches on tissue specimens and plasma samples classified based on pathological characteristics. Patients with carotid-unstable plaques exhibited elevated plasma concentrations of MD-1 (LY86), while patients with stable plaques demonstrated comparatively lower levels. Furthermore, soluble MD-1 was found to induce the formation of NETs through activation of Toll-like receptor signaling pathway. The proliferative and immature vascularization effects of NETs on endothelial cells, as well as their inhibitory impact on cell migration, are directly correlated with the concentration of NETs. Additionally, NETs were found to activate the NF-κB signaling pathway, thereby upregulating ICAM1, VCAM1, MMP14, VEGFA, and IL6 expression in both Human umbilical vein endothelial cells (HUVECs) and HAECs. Subsequently, a significant increase in intraplaque neovascularization by NETs results in poor carotid plaque stability, and NETs in turn stimulate macrophages to produce more MD-1, generating a harmful positive feedback loop. Our findings suggest that soluble MD-1 in the bloodstream triggers the production of NETs through activation of the Toll-like receptor signaling pathway and further indicate NETs mediate a crosstalk between the microenvironment of the carotid plaque and the neovascularization of the intraplaque region. Inhibiting NETs formation or MD-1 secretion may represent a promising strategy to effectively suppress the development of unstable carotid plaques.

Abstract ARHGAP25, a member of the ARHGAP family, encodes a negative regulator of Rho-GTPase that is important for actin remodeling, cell polarity, and cell migration. ARHGAP25 is down-regulated in a variety of solid tumors and promotes cancer cell growth, migration, and invasion. However, nothing is understood about ARHGAP25’s biological function in osteosarcoma. This work used qPCR and WB to confirm the expression of ARHGAP25 in osteosarcoma following the initial analysis of its expression in pan-cancer. For GO and KEGG analysis, we have chosen 300 genes from the TARGET osteosarcoma data that had the strongest positive correlation with ARHGAP25, and we created nomogram and calibration charts. We simultaneously overexpressed ARHGAP25 in osteosarcoma cells to examine its impact on apoptosis and proliferation. By using MSP, we determined their methylation status in osteosarcoma cells and normal bone cells. We observed that ARHGAP25 was significantly downregulated in a range of malignancies, including osteosarcoma, and was associated with poor patient outcomes. The decrease of ARHGAP25 expression in osteosarcoma is related to DNA methylation. Overexpression of ARHGAP25 induced apoptosis and inhibited the proliferation of osteosarcoma cells in vitro. In addition, ARHGAP25 is also associated with immune-related pathways in osteosarcoma. These findings suggest that ARHGAP25 is a valuable prognostic biomarker in osteosarcoma patients.

Abstract Background Residual symptoms of depressive disorders are serious health problems. However, the progression process is hardly predictable due to high heterogeneity of the disease. This study aims to: (1) classify the patterns of changes in residual symptoms based on homogeneous data, and (2) identify potential predictors for these patterns. Methods In this study, we conducted a data-driven Latent Class Growth Analysis (LCGA) to identify distinct tendencies of changes in residual symptoms, which were longitudinally quantified using the QIDS-SR16 at baseline and 1/3/6 months post-baseline for depressed patients. The association between baseline characteristics (e.g. clinical features and cognitive functions) and different progression tendencies were also identified. Results The tendency of changes in residual symptoms was categorized into four classes: “light residual symptom decline (15.4%)”, “residual symptom disappears (39.3%)”, “steady residual symptom (6.3%)” and “severe residual symptom decline (39.0%)”. We observed that the second class displayed more favorable recuperation outcomes than the rest of patients. The severity, recurrence, polypharmacy, and medication adherence of symptoms are intricately linked to the duration of residual symptoms’ persistence. Additionally, clinical characteristics including sleep disturbances, depressive moods, alterations in appetite or weight, and difficulties with concentration have been identified as significant factors in the recovery process. Conclusions Our research findings indicate that certain clinical characteristics in patients with depressive disorders are associated with poor recovery from residual symptoms following acute treatment. This revelation holds significant value in the targeted attention to specific patients and the development of early intervention strategies for residual symptoms accordingly.

Abstract The efficacy of immunotherapy for clear cell renal cell carcinoma (ccRCC), especially advanced ccRCC, is limited, presenting a clinical challenge. This limitation is closely tied to the immune regulation network. Understanding the heterogeneity of the tumour microenvironment (TME) is crucial for developing advanced ccRCC therapies. Using publicly available ccRCC data (scRNA-seq, bulk RNA-seq, and somatic mutation data), a multiomics study was performed to explore TME heterogeneity. Three distinct ccRCC immune subtypes were identified through combined scRNA-seq and bulk RNA-seq analysis. A prognostic model based on unique cell signalling molecules in immunosuppressive tumour subtype was validated in the TCGA and CheckMate cohorts. MDK emerged as a critical regulatory gene in the immunosuppressive subtype, predicting a poor ccRCC prognosis and a poor immunotherapy response. MDK promotes M2 macrophage polarization via the MDK-LRP1 interaction, and the inhibition of MDK suppressed M2 polarization. This study revealed the heterogeneity of the ccRCC TME and a reliable prognostic model, shedding light on the vital role of MDK in the immunosuppressive TME and paving the way for optimized ccRCC immunotherapy.

Abstract Improvements in the polarization of environmentally-friendly perovskite ferroelectrics have proved to be a challenging task in order to replace the toxic Pb-based counterparts. In contrast to common methods by complex chemical composition designs, we have formed Mn-inlaid antiphase boundaries in Mn-doped (K,Na)NbO3 thin films using pulsed laser deposition method. Here, we observed that mono- or bi-atomic layer of Mn has been identified to inlay along the antiphase boundaries to balance the charges originated from the deficiency of alkali ions and to induce the strain in the KNN films. Thus, rectangular saturated polarization-electric field hysteresis loops have been achieved, with a significantly improved twice remanent polarization of 114 μC/cm2 with an applied electric field of 606 kV/cm, which can be comparable to that of the typical Pb-based thin films. Moreover, we directly see the Mn occupation at the A-site of KNN perovskite structure using atomic-scale microstructure and composition analysis. The Mn-inlaid antiphase boundary can further enrich the understanding of perovskite crystal structure and give more possibilities for the design and optimization of perovskite materials.

Abstract Ultrasonic scalpel design for minimally invasive surgical procedures is mainly focused on optimizing cutting performance. However, an important issue is the low fatigue life of traditional ultrasonic scalpels, which affects their long-term reliability and effectiveness and creates hidden dangers for surgery. In this study, a multi-objective optimal design for the cutting performance and fatigue life of ultrasonic scalpels was proposed using finite element analysis and fatigue simulation. The optimal design parameters of resonance frequency and amplitude were determined. By setting the transition fillet and keeping the gain structure away from the node position to enable the scalpel to have a high service life with excellent cutting performance. The frequency modulation method of setting the vibration node bosses at the node position and setting the vibration antinode grooves at the antinode position was compared. Then, the mechanism of the influence of various design elements, such as tip, shank, node position, and antinode position, on the resonance frequency, amplitude, and fatigue life of the ultrasonic scalpel was analyzed, and the optimal design principles of the ultrasonic scalpel were obtained. The proposed ultrasonic scalpel design was confirmed by simulations, impedance measurements, and liver tissue cutting experiments, demonstrating its feasibility and enhanced performance. This research introduces innovative design strategies to improve the fatigue life and performance of ultrasonic scalpels to address an important issue in minimally invasive surgery.

Abstract Prognostics and health management (PHM) has gotten considerable attention in the background of Industry 4.0. Battery PHM contributes to the reliable and safe operation of electric devices. Nevertheless, relevant reviews are still continuously updated over time. In this paper, we browsed extensive literature related to battery PHM from 2018 to 2023 and summarized advances in battery PHM field, including battery testing and public datasets, fault diagnosis and prediction methods, health status estimation and health management methods. The last topic includes state of health estimation methods, remaining useful life prediction methods and predictive maintenance methods. Each of these categories is introduced and discussed in details. Based on this survey, we accordingly discuss challenges left to battery PHM, and provide future research opportunities. This research systematically reviews recent research about battery PHM from the perspective of key PHM steps and provide some valuable prospects for researchers and practitioners.

Abstract Background This study aimed to assess the impact of coronavirus disease 2019 (COVID-19) on hospital service utilization and revenue in Chinese tertiary hospitals and develop an optimal pandemic control strategy (OPCS) for the peak period of the Omicron wave. Methods Retrospective data from three Chinese tertiary hospitals (provincial, city, and county level) were analyzed for three phases: pre-outbreak (Jan-Apr 2019), outbreak (Jan-Apr 2020), and post-outbreak (Jan-Apr 2021). OPCS was developed under the guidance of the China government pandemic control policy during post-break phase of COVID-19. A decision-tree model was constructed to compare OPCS to strict pandemic control strategy during outbreak phase for the hospital service utilization and hospital revenue in a provincial tertiary hospital during the Omicron wave. Results Outpatient, emergency room (ER) visits, hospitalizations, and intensive care admissions dropped by 33.8–53.4% during the outbreak, with the provincial hospital being the most affected. Hospital revenue also declined, especially for the provincial hospital (40.1%). Post-outbreak, most services recovered, but ER visits remained lower (11.6% decrease for provincial hospital, 46.5% for county hospital). Total income and expenditure decreased, with the provincial hospital experiencing the most significant revenue reduction (45.7%). OPCS showed greater utilization of medical services (31.6 times more outpatient visits; 1.7 times more inpatient days; 3.4% more surgery volume) and higher revenue (¥220.8 million more) compared to the strict pandemic control strategy. Conclusions COVID-19 measures were associated with less hospital service utilization and revenue in Chinese tertiary hospitals. The developed OPCS in Chinese tertiary hospitals, focusing on isolating infected inpatients but not shutting down the hospital facilities exposed to virus, could be effective in optimizing hospital service utilization and hospital revenue during the Omicron wave.