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Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response. Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific, particularly involving the corticolimbic system, including the ventral tegmental area, nucleus accumbens, prefrontal cortex, amygdala, and hippocampus. Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology. In this review, we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression. We focused on associated molecular pathways and neural circuits, with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit. We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature, severity, and duration of stress, especially in the above-mentioned brain regions of the corticolimbic system. Therefore, BDNF might be a biological indicator regulating stress-related processes in various brain regions.

BackgroundOsteonecrosis of the jaw (ONJ) stands as a severe complication linked to the use of bisphosphonates, particularly zoledronic acid, which is widely prescribed for managing conditions like osteoporosis and bone metastasis. This study is geared towards the development and validation of a clinical prediction model for ONJ in patients undergoing zoledronic acid treatment.MethodsWe harnessed data from the FDA Adverse Event Reporting System (FAERS) as our training dataset, while the Canada Vigilance Adverse Reaction (CVAR) database served as the testing dataset. The study encompassed patients treated with zoledronic acid and subsequently diagnosed with ONJ. We analysed a range of predictive factors, including breast cancer, bone metastasis, osteoporosis, vitamin D and calcium levels, comorbidities, the number of concomitant medications, dosage, age, weight, and gender. Logistic regression and nomogram analysis were the chosen methodologies for constructing the predictive model. To evaluate the model’s performance, we utilized receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).ResultsThe study encompassed a total of 2,126 patients in the training cohort, 911 patients in the internal test cohort from the FAERS database, and 121 patients in the external test cohort from the CVAR database. Notable predictors for ONJ included bone metastasis (OR: 1.65, 95% CI: 1.22–2.24), osteoporosis (OR: 0.33, 95% CI: 0.21–0.52), the number of concomitant medications (OR: 1.07, 95% CI: 1.05–1.09), and the dosage of zoledronic acid (OR: 1.24, 95% CI: 1.10–1.39). The nomogram exhibited robust discriminatory power, evidenced by an area under the curve (AUC) of 0.77 in the training cohort, 0.76 in the internal test cohort, and 0.90 in the external test cohort. Calibration plots demonstrated a strong alignment between observed and predicted probabilities. Furthermore, DCA highlighted the prediction model’s significant net benefit across various threshold probabilities.ConclusionBy leveraging data from both the FAERS and Canadian databases, this study has successfully developed and validated a clinical prediction model for ONJ in patients receiving zoledronic acid. This model stands as a valuable tool for clinicians, enabling them to pinpoint high-risk patients and make evidence-based treatment decisions to minimize the risk of ONJ.

In response to the challenges posed by climate change, China has launched the Personal Carbon Inclusion (PCI) scheme to encourage individuals to transition towards low-carbon lifestyles. This study investigates the behaviors of participants within the PCI scheme using a tripartite evolutionary game model, encompassing high-income and low-income individuals, as well as the PCI platform itself. The research analyzes participants' strategies, examines the evolutionary stability of different strategies, and assesses the robustness of equilibrium points within the game dynamics. Key findings reveal: (1) High-income participants tend to be less willing to adopt low-carbon behaviors compared to low-income participants. (2) The PCI platform displays limited proactive engagement in promoting low-carbon policies. (3) Factors, particularly the cost and pricing mechanisms of low-carbon actions, significantly impact the evolutionary progression of the system. Moreover, practical recommendations are provided to enhance the effectiveness of PCI schemes.

Abstract In this study, we aimed to study the role of TCONS_00006091 in the pathogenesis of oral squamous cellular carcinoma (OSCC) transformed from oral lichen planus (OLP). This study recruited 108 OSCC patients which transformed from OLP as the OSCC group and 102 OLP patients with no sign of OSCC as the Control group. ROC curves were plotted to measure the diagnostic values of TCONS_00006091, miR-153, miR-370 and let-7g, and the changes in gene expressions were measured by RT-qPCR. Sequence analysis and luciferase assays were performed to analyze the molecular relationships among these genes. Cell proliferation and apoptosis were observed via MTT and FCM. TCONS_00006091 exhibited a better diagnosis value for OSCC transformed from OLP. OSCC group showed increased TCONS_00006091 expression and decreased expressions of miR-153, miR-370 and let-7g. The levels of SNAI1, IRS and HMGA2 was all significantly increased in OSCC patients. And TCONS_00006091 was found to sponge miR-153, miR-370 and let-7g, while these miRNAs were respectively found to targe SNAI1, IRS and HMGA2. The elevated TCONS_00006091 suppressed the expressions of miR-153, miR-370 and let-7g, leading to the increased expression of SNAI1, IRS and HMGA2. Also, promoted cell proliferation and suppressed apoptosis were observed upon the over-expression of TCONS_00006091. This study demonstrated that the expressions of miR-153, miR-370 and let-7g were down-regulated by the highly expressed TCONS_00006091 in OSCC patients, which accordingly up-regulated the expressions of SNAI1, IRS and HMGA2, resulting in the promoted cell proliferation and suppressed cell apoptosis.

Objective: Double-J (DJ) ureteric stents are commonly placed perioperatively for semirigid or flexible ureteroscopic renal surgery. It is believed that lesser stent material within the bladder mitigates stent-related symptoms. This study aimed to evaluate the J-Fil ureteral stent, a single pigtail suture stent compared with conventional DJ stent in relation to stent symptoms in an Asian population undergoing ureterorenal intervention. Methods: Based on internal audit committee recommendation approval, the records of 50 patients retrieved, available data of 41 patients who were prospectively enrolled into two groups (Group 1 [J-Fil stent group], n=21 and Group 2 [DJ stent group], n=20) between August 2020 to January 2021, were analysed. Parameters compared were nature of procedure, stone location and size, ease of deployment or removal, and complications. A modified universal stent symptom questionnaire was used to assess morbidity of stent symptoms within 48 h of insertion and at removal. Results: Both groups had similar median age, distribution in male to female ratio, and stone size. The overall median universal stent symptom questionnaire score at insertion was similar for bladder pain, flank or loin pain, and quality of life between Group 1 and 2; however, at removal Group 1 fared significantly better than Group 2, especially for flank or loin pain and pain at voiding. Both groups had similar ease in insertion with no hospital readmissions. Conclusion: Our audit favoured the single pigtail suture stent in Asian ureters in mitigating stent-related issues. It showed a good safety profile with easy deployment and removal. It promises a new standard in stenting.

Abstract The mix proportion of multi-source coal-based solid waste (CSW) for underground backfilling affects transportation and support performance of backfill materials, and even the backfilling cost. In this study, the optimal mix proportion of desulfurization gypsum (DG), furnace bottom slag (FBS) and gasification fine slag (GFS) is determined by the Response Surface Methodology–Box Behnken Design (RSM-BBD). Then the fluidity, bleeding rate, 3-day strength, 7-day strength and preparation cost are evaluation indicators, the optimal mix proportion of backfill materials is determined by the multi-objective decision-making method (MDM). Finally, the microstructure of the backfill material with optimal mix proportion was studied by TGA, MIP, SEM–EDS and XRD. The results show that the mix proportion of CSW with the optimal comprehensive index is coal gangue (CG): coal fly ash (CFA): DG: FBS: GFS = 1:1.5:0.2:0.1:0.1, the mass concentration is 78%, and ordinary Portland cement (OPC)/CSW = 7.5%. The weight loss phenomenon of the backfill material with the optimal mix proportion occurs continuously during the heating process, mainly due to the evaporation of crystal water, structural water and hydroxyl water. There are dense narrow-necked pores in the backfill material, and the pore connectivity is poor. There is no hydration reaction occurs between CSW particles, and the strength increase of the backfill material mainly depends on the hydration reaction of cement. In ettringite, part of Al2O3 is replaced by SiO2, and part of CaSO4 is replaced by CaCO3. This study provides a reference for the engineering application of underground backfilling with multi-source CSW.

Cancer is a complex and multifaceted group of diseases characterized by uncontrolled cell growth that leads to the formation of malignant tumors. Recent studies suggest that N6-methyladenosine (m6A) RNA methylation plays pivotal roles in cancer pathology by influencing various cellular processes. However, the degree to which these mechanisms are shared across different cancer types remains unclear. In this study, we analyze an expansive array of 167 m6A epitranscriptome profiles covering 12 distinct cancer types and their originating normal tissues. We trained 12 distinct, cancer type-specific interpretable deep cross network models, which successfully distinguish between specific pairs of normal and cancer m6A contexts using integrated information from both the sequences and curated genomic knowledge. Interestingly, cross-cancer type testing indicated the existence of shared genomic patterns across various cancers at the epitranscriptome level. A pan-cancer model was subsequently developed to identify these shared patterns that could not be observed in a single cancer type. Our analysis uncovered, for the first time, a common epitranscriptome signature shared across multiple cancer types, particularly associated with RNA hybridization process and aberrant splicing. This highlights the importance of a comprehensive understanding of the pan-cancer epitranscriptome and holding potential implications in the development of RNA methylation-based therapeutics for various cancers.

Background In liquid biopsy, mutation detection is primarily performed using cell-free DNA (cfDNA). However, the numerous advantages of extracellular vesicle (EV) DNA for mutation detection have gradually garnered the attention of researchers in recent years. This study aimed to compare the differences between EV DNA and cfDNA in mutation detection and explore the role of plasma androgen receptor (AR) mutations in the prognosis of prostate cancer (PCa).Methods We compared the biological characteristics of plasma extracellular vesicle DNA (p-EV DNA) and cfDNA by capillary electrophoresis and concentration detection. Subsequently, we performed pan-oncogene-targeted sequencing in paired tissue and plasma samples from five patients with PCa to verify the feasibility of mutation detection using p-EV DNA and cfDNA. Further, we conducted AR mutation detection in expanded samples to compare the differences between EV DNA and cfDNA in mutation detection and to analyse their role in PCa.Results p-EV DNA fragments were larger than plasma cell-free DNA (p-cfDNA) fragments; however, there was no significant difference in their concentrations in the plasma of patients with PCa. Feasibility analysis revealed that major mutations associated with PCa detected in tissue samples could be identified in both p-EV DNA and p-cfDNA. Advantage comparison found that, although cfDNA could detect more mutations, AR mutations in EV DNA were more strongly associated with a poor prognosis of PCa than cfDNA.Conclusion Mutation detection using either EV DNA or cfDNA is both feasible in PCa liquid biopsies, and EV DNA AR mutations have an advantage in prognostic assessment for PCa. This study lays the foundation for future research on EV DNA-related biomarkers.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic, posing serious threats to global health. Effective broad-spectrum antiviral drugs for the treatment of COVID-19 are not sufficiently available. In the present study, we investigated the antiviral activity of the natural lignan diphyllin (PubChem CID 100492) against different SARS-CoV-2 variants and explored the underlying molecular mechanisms. We found that diphyllin dose-dependently inhibits the SARS-CoV-2 spike (S)-mediated entry into different types of cells. The potent inhibition was evident against spike proteins derived from the original SARS-CoV-2 and from variants of concern such as Alpha, Beta, Delta or Omicron. Accordingly, diphyllin also significantly inhibited the in vitro infection of a clinical SARS-CoV-2 virus isolate. Mechanistically, diphyllin simultaneously inhibited the endosomal entry of SARS-CoV-2 by neutralizing the endosomal acidification and reducing the activity of the cysteine protease cathepsin L (CTSL) as well as S-meditated cell surface entry by impairing furin activity. Collectively, our findings establish diphyllin as novel inhibitor of CTSL and furin proteases, resulting in a double-pronged attack on SARS-CoV-2 entry along endosomal as well as cell surface routes. Therefore, diphyllin has the potential to be advanced as an inhibitor of SARS-CoV-2 entry.

Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized. We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated. A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases. In summary, AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.

Abstract Our current knowledge regarding the distribution patterns of ancient and recent recycled materials, as well as the origin of intraplate basalts in the eastern Asia Big Mantle Wedge (BMW), is limited. To address this, we conducted a detailed geochemical analysis of olivine melt inclusions (OLMI) in nephelinite samples. The normal OLMIs detected in our investigation exhibit geochemical features that closely resemble those of the hosting nephelinite, indicating a consistent association with a carbonated mantle source. Additionally, we identified a distinct group of anomalous OLMIs that displayed different geochemical characteristics from the hosting nephelinite but showed similarities to regional alkali basalts sourced from pyroxenite. The observed geochemical diversity in the nephelinite OLMIs suggests an interaction between deeply derived carbonated melts originating from the flattened Pacific slab in the mantle transition zone and pyroxenite in the lithospheric mantle. Carbonated fluid‐fluxed melting is key to basalt formation in the BMW.

Abstract Background Acupuncture as a traditional Chinese medicine therapy relies on unique theories to alleviate fatigue. The aim of this study is to evaluate the effect of acupuncture on exercise‐induced fatigue utilizing transcranial magnetic stimulation (TMS). Methods A total of 20 participants with regular exercise habits were recruited for this study. All participants were randomly assigned to receive either acupuncture or sham acupuncture intervention for exercise‐induced fatigue. TMS and a heart rate monitor were used to measure the amplitude and latency of motor evoked potential (MEP) as well as heart rate every 5 min over a 30‐min period. The blood lactic acid (BLA) levels were measured using Lactate Scout+ at baseline, 0 min, and 30 min after fatigue. Two‐way repeated measures analysis of variance was utilized to compare the differences between the effects of acupuncture method and time. Bonferroni post hoc tests were conducted to compare specific differences. Statistical significance was set at p

Single-pixel imaging is an advanced computational imaging technique based on compressive sensing that offers higher signal-to-noise ratio and broader application scope compared to traditional imaging techniques. However, conventional reconstruction algorithms suffer from issues such as long processing time and low reconstruction accuracy during the sampling and reconstruction processes. Deep learning-based compressed reconstruction networks can circumvent the complex iterative computations of traditional algorithms and achieve fast, high-quality reconstruction. In this paper, we propose a Variational Multi-Scale Error Compensation Network (VMSE) based on variational autoencoders. VMSE designs an error compensation network to enhance the feature representation capability of the sampling reconstruction network. We employ multiple latent variables to generate error features at different scales in the intermediate layers of the error compensation network, compensating the reconstructed image. Additionally, we design a module that simultaneously learns in the spatial and frequency domains, which is used for upsampling and complementing the missing high-frequency information in the frequency domain. On the MNIST dataset, when the sampling rate is 0.025, VMSE achieved higher Peak Signal-to-Noise Ratio(PSNR) and Structural Similarity Index(SSIM) scores, especially with an SSIM score of 0.963, significantly surpassing Reconnet and DR2Net's scores of 0.930 and 0.920, respectively. This was further corroborated by practical experiments, where at low sampling rates, VMSE could reconstruct outlines more clearly compared to TVAL3.

Abstract Background Cortical buttress are important factors for postoperative stable reconstruction of per/inter-trochanteric fractures. The study aimed to measure the remnant axial cortical length (RACL) of the proximal circumference of the femur, and to determine which part of the RACL can be used reliably to postoperatively sustain the head–neck fragment as a cortical support pattern. Methods Eighty patients with trochanteric hip fractures admitted from January 2015 to January 2016 were included in a retrospective study. Their pre-operative computed tomography (CT) images were used to form 3D-CT reconstructions via Mimics software. After simulated rotation and movement for fracture reduction, the RACL, its three component parts—namely, the remnant anterior cortex (RAC), remnant lateral cortex (RLC), and remnant posterior cortex (RPC) —the γ angle between the anterior and posterior cortex, and the Hsu’s lateral wall thickness (LWT) were evaluated. Results Patients with an A1 fracture (21/80) had a longer RACL (88.8 ± 15.8 mm) than those with an A2 fracture (60.0 ± 11.9 mm; P

Polysaccharides from hemp seeds exhibit antioxidant activities in vitro and in vivo. However, crude polysaccharide quality is often low owing to the presence of fibres and pigment impurities, which are difficult to eliminate in the hemp seed shell. In this study, crude polysaccharides from hemp kernels (HKP) were obtained by hot water extraction and separated by membrane ultrafiltration into eight fractions with different molecular weights. Total antioxidant capacity and free radical scavenging (DPPH) assays were performed to evaluate the antioxidant activities of HKP and the fractions in vitro. The structural characteristics of HKP were determined using various analytical techniques. The Fe3+-reducing power of HKP was 7.65 ± 0.22 μmol/g, and HKP possessed the highest DPPH radical-scavenging rates (94.30 ± 2.27%), similar to 5 mg/mL Vitamin C (Vc), which had a rate of 95%. The HKP was an acidic polysaccharide with a low molecular weight (4.21 ± 0.12 kDa). The monosaccharide composition indicated that HKP primarily comprised mannose, ribose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose, and fucose in a molar ratio of 0.96:1.95:8.27:0.98:9.46:1.69:6.10:2.82. The molar mass of HKP was distributed widely in a triple helical conformation. This study provides a scientific basis for further research on the use of hemp polysaccharides.

Abstract Senile plaque, composed of amyloid β protein (Aβ) aggregates, is a critical pathological feature in Alzheimer's disease (AD), leading to cognitive dysfunction. However, how Aβ aggregates exert age‐dependent toxicity and temporal cognitive dysfunction in APP/PS1 mice remains incompletely understood. In this study, we investigated AD pathogenesis and dynamic alterations in lysosomal pathways within the hippocampus of age‐gradient male mice using transcriptome sequencing, molecular biology assays, and histopathological analyses. We observed high levels of β‐amyloid precursor protein (APP) protein expression in the hippocampus at an early stage and age‐dependent Aβ deposition. Transcriptome sequencing revealed the enrichment of differential genes related to the lysosome pathway. Furthermore, the protein expression of ATP6V0d2 and CTSD associated with lysosomal functions exhibited dynamic changes with age, increasing in the early stage and decreasing later. Similar age‐dependent patterns were observed for the endosome function, autophagy pathway, and SGK1/FOXO3a pathway. Nissl and Golgi staining in the hippocampal region showed age‐dependent neuronal loss and synaptic damage, respectively. These findings clearly define the age‐gradient changes in the autophagy–lysosome system, the endosome/lysosome system, and the SGK1/FOXO3a pathway in the hippocampus of APP/PS1 mice, providing new perspectives and clues for understanding the possible mechanisms of AD, especially the transition from compensatory to decompensated state.

Bioactive non-woven dressings can be prepared by dip coating of non-woven cloth in solutions containing bioactive polyethylene bearing pendant arms of polyethylene (PE5000) and modified PEG3400-biomolecules including linear Arg-Gly-Asp (RGD), collagen fragment (Gly-Pro-Hyp)3, laminin-derived peptide (AGQWHRVSVRWGC) (A5G81) and hyaluronic acid (HA). Obtainment of ultimate coating concentration for each type of non-woven cloth is achieved such that the technically demanding bioactive polyethylene does not delaminate from the non-woven cloth itself but is of sufficient quantity for bioactivity. Scanning electron microscopy images show uniform polyethylene deposition on the non-woven cloth. Good water absorption and permeability allow the use of such bioactive polyethylene coated non-woven cloth as wound dressings. Material biocompatibility is demonstrated using in vitro human skin fibroblast assays. In vivo porcine full thickness excisional wound model shows PE5000-coated non-woven cloth can remarkably accelerate skin regeneration to close the wounds faster than clinical gold standard dressing. Thus, the results presented here may provide a promising guide for bioactive polyethylene-modified non-woven materials for wound dressing applications.

IntroductionRecently, the microstate analysis method has been widely used to investigate the temporal and spatial dynamics of electroencephalogram (EEG) signals. However, most studies have focused on EEG at resting state, and few use microstate analysis to study emotional EEG. This paper aims to investigate the temporal and spatial patterns of EEG in emotional states, and the specific neurophysiological significance of microstates during the emotion cognitive process, and further explore the feasibility and effectiveness of applying the microstate analysis to emotion recognition.MethodsWe proposed a KLGEV-criterion-based microstate analysis method, which can automatically and adaptively identify the optimal number of microstates in emotional EEG. The extracted temporal and spatial microstate features then served as novel feature sets to improve the performance of EEG emotion recognition. We evaluated the proposed method on two publicly available emotional EEG datasets: the SJTU Emotion EEG Dataset (SEED) and the Database for Emotion Analysis using Physiological Signals (DEAP).ResultsFor the SEED dataset, 10 microstates were identified using the proposed method. These temporal and spatial features were fed into AutoGluon, an open-source automatic machine learning model, yielding an average three-class accuracy of 70.38% (±8.03%) in subject-dependent emotion recognition. For the DEAP dataset, the method identified 9 microstates. The average accuracy in the arousal dimension was 74.33% (±5.17%) and 75.49% (±5.70%) in the valence dimension, which were competitive performance compared to some previous machine-learning-based studies. Based on these results, we further discussed the neurophysiological relationship between specific microstates and emotions, which broaden our knowledge of the interpretability of EEG microstates. In particular, we found that arousal ratings were positively correlated with the activity of microstate C (anterior regions of default mode network) and negatively correlated with the activity of microstate D (dorsal attention network), while valence ratings were positively correlated with the activity of microstate B (visual network) and negatively correlated with the activity of microstate D (dorsal attention network).DiscussionIn summary, the findings in this paper indicate that the proposed KLGEV-criterion-based method can be employed to research emotional EEG signals effectively, and the microstate features are promising feature sets for EEG-based emotion recognition.

Abstract Background Metastasis is still a major cause of poor pathological outcome and prognosis in esophageal squamous cell carcinoma (ESCC) patients. NUAK1 has been reported highly expressed in many human cancers and is associated with the poor prognosis of cancer patients. However, the role of NUAK1 and its underlying signaling mechanism in ESCC metastasis remain unclear. Methods Expression of NUAK1 in ESCC was detected by real-time quantitative RT-PCR (qRT-PCR), Western blotting and immunohistochemical staining. MTT, colony formation, wound-healing and transwell assays were used to determine the role NUAK1 in vitro. Metastasis was evaluated by use of an experimental pulmonary metastasis model in BALB/c-nu/nu mice. The mechanisms were assessed by using coimmunoprecipitation, immunofluorescence and dual-luciferase reporter gene experiments. Results NUAK1 was highly expressed in ESCC tissues compared with the adjacent normal esophageal epithelial tissues. Moreover, the elevated expression of NUAK1 positively correlated with tumor invasion depth, lymph node metastasis, pathological TNM stage, and poor survival in ESCC patients. Further experiments showed that NUAK1 overexpression did not change the cell viability and colony formation of ESCC cells, while remarkably promoted the migration and invasion in vitro and experimental pulmonary metastasis in vivo. Mechanistically, NUAK1 enhanced the transcription level of Slug, which enhanced the migratory and invasive capability of ESCC cells. Consistently, silencing Slug almost completely diminished the migration and invasion of NUAK1-overexpressing ESCC cells. Further studies demonstrated that NUAK1 upregulated the transcription activity of Slug through activating the JNK/c-Jun pathway. Conclusion These results demonstrated that NUAK1 promoted the metastasis of ESCC cells through activating JNK/c-Jun/Slug signaling, indicating NUAK1 is a promising therapeutic target for metastatic ESCC.

Bi3+ doped Ti/Sb-SnO2/PbO2 electrode materials were fabricated by electrodeposition to improve their electrochemical performance in zinc electrowinning. The surface morphology, chemical composition, and hydrophilicity of the as-prepared electrodes were characterized using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and contact angle. An electrochemical measurement and an accelerated lifetime experiment were also conducted to investigate the electrocatalytic performance and stability of the electrodes. The results show that the Bi3+ modification electrode has an important effect on the coating morphology, the crystal structure, the surface hydrophilicity, the electrocatalytic activity, and the stability. The electrode prepared from the solution containing 2 mmol·L−1 Bi(NO3)3 (marked as the Ti/Sb-SnO2/2Bi-PbO2 electrode) exhibits the best hydrophilicity performance (θ = 21.6°) and the longest service life (1196 h). During the electrochemical characterization analysis, the Ti/Sb-SnO2/2Bi-PbO2 electrode showed the highest oxygen evolution activity, which can be attributed to it having the highest electroactive surface (qT* = 21.20 C·cm−2) and the best charge-transfer efficiency. The DFT calculation demonstrated that the doping of Bi3+ leads to a decrease in the OER reaction barrier and an increase in the DOS of the electrode, which further enhances the catalytic activity and the conductivity of the electrode. Moreover, the simulated zinc electrowinning experiment demonstrated that the Ti/Sb-SnO2/2Bi-PbO2 electrode consumes less energy than other electrodes. Therefore, it is expected that the Bi3+ modified electrode will become a very promising electrode material for zinc electrowinning in the future.

Chlorinated volatile organic compounds (CVOCs) are persistent pollutants and harmful to the atmosphere, environment, and human health. The catalytic elimination of CVOCs has become a hotspot of interest due to their self-toxicity, the secondary generation of chlorinated by-products, and the Cl poisoning of catalysts. The development of high-performance, highly selective, and anti-poisoning catalysts is a critical issue. Bimetallic catalysts exhibit an improved dechlorination performance, poisoning resistance, and product selectivity through the modulation of geometrical and electronic structures. The present review article gives a brief overview of the recent advancements in the preparation of bimetallic catalysts and their catalytic CVOC elimination activities. In addition, representative case studies are provided to investigate the physicochemical properties, CVOC conversion, COx and inorganic chlorine species selectivities, and by-product control so that the structure–performance relationships of bimetallic catalysts can be established. Furthermore, this review article provides a fundamental understanding of designing bimetallic catalysts with specific active components and the desired physicochemical properties for target reactions. In the end, related perspectives for future work are proposed.

As the most pervasive epigenetic marker present on mRNAs and long non-coding RNAs (lncRNAs), N6-methyladenosine (m6A) RNA methylation has been shown to participate in essential biological processes. Recent studies have revealed the distinct patterns of m6A methylome across human tissues, and a major challenge remains in elucidating the tissue-specific presence and circuitry of m6A methylation. We present here a comprehensive online platform, m6A-TSHub, for unveiling the context-specific m6A methylation and genetic mutations that potentially regulate m6A epigenetic mark. m6A-TSHub consists of four core components, including (1) m6A-TSDB, a comprehensive database of 184,554 functionally annotated m6A sites derived from 23 human tissues and 499,369 m6A sites from 25 tumor conditions, respectively; (2) m6A-TSFinder, a web server for high-accuracy prediction of m6A methylation sites within a specific tissue from RNA sequences, which was constructed using multi-instance deep neural networks with gated attention; (3) m6A-TSVar, a web server for assessing the impact of genetic variants on tissue-specific m6A RNA modifications; and (4) m6A-CAVar, a database of 587,983 The Cancer Genome Atlas (TCGA) cancer mutations (derived from 27 cancer types) that were predicted to affect m6A modifications in the primary tissue of cancers. The database should make a useful resource for studying the m6A methylome and the genetic factors of epitranscriptome disturbance in a specific tissue (or cancer type). m6A-TSHub is accessible at www.xjtlu.edu.cn/biologicalsciences/m6ats.

Abstract In order to deeply study the basic characteristics, diffusion laws, and flow laws of coal gangue and coal gangue slurry, the basic characteristic parameters of coal gangue and coal gangue slurry were obtained through particle size distribution test, electron microscope scanning test, X-ray diffraction test, X-ray fluorescence spectrum test, and angle of repose test. The conveying performance test of coal gangue slurry was carried out, and based on this, a simulation test of coal gangue slurry caving areas was designed. The diffusion and flow laws of coal gangue slurry under the same inclination angle were summarized, and the field test of fluidization filling in the caving areas was conducted. The results show that: (1) The water-to-gangue ratio was the main controlling factor for the conveying performance of coal gangue slurry. The extensibility, slump, and bleeding rate of the coal gangue slurry increased with the increase of the water-to-gangue ratio. (2) The diffusion profile of coal gangue slurry at different dip angles was arc-shaped, and the diffusion distance of slurry increased with the increase of infiltration time. However, there were differences in the sustained diffusion ability of different dip angles. (3) At the same time interval, the spatial accumulation patterns of scattered gangue in different regions will lead to differences in the diffusion speed of the slurry. (4) Both burying and hanging pipes in the falling area can safely and efficiently fill the gangue slurry. The diffusion distance of the caving areas in the test working face was basically consistent with the diffusion distance of the slurry in the simulation test of the coal gangue slurry caving areas.

Abstract Background/aims To investigate the clinical situation, treatment methods, and clinical predictors of surgical intervention in children with magnetic foreign bodies in the digestive tract. Materials and methods From January 2019 to June 2022, we retrospectively analyzed the clinical data of 72 children who ingested magnetic foreign bodies inadvertently in our hospital, including their general information, admissions, clinical manifestations, and treatment methods, as well as pertinent literature and statistical data. Following software processing, univariate and multivariate logistic regression analyses were conducted to determine the independent risk factors of this study. Results In this study, 16 patients (22.2%) were discharged smoothly following conservative treatment and 19 patients (26.4%) were cured by gastroscopy. The remaining 37 patients (51.4%) were underwent surgery, in which 26 cases developed gastrointestinal perforation. There were statistical differences between surgery group and non- surgery group in the days of eating by mistake, clinical manifestations (nausea and vomiting, intermittent abdominal pain, abdominal muscle tension) and movement trajectory by every 24-h radiograph (P

Abstract In vitro, ACE2 translocates to the nucleus to induce SARS-CoV-2 replication. Here, using digital spatial profiling of lung tissues from SARS-CoV-2-infected golden Syrian hamsters, we show that a specific and selective peptide inhibitor of nuclear ACE2 (NACE2i) inhibits viral replication two days after SARS-CoV-2 infection. Moreover, the peptide also prevents inflammation and macrophage infiltration, and increases NK cell infiltration in bronchioles. NACE2i treatment increases the levels of the active histone mark, H3K27ac, restores host translation in infected hamster bronchiolar cells, and leads to an enrichment in methylated ACE2 in hamster bronchioles and lung macrophages, a signature associated with virus protection. In addition, ACE2 methylation is increased in myeloid cells from vaccinated patients and associated with reduced SARS-CoV-2 spike protein expression in monocytes from individuals who have recovered from infection. This protective epigenetic scarring of ACE2 is associated with a reduced latent viral reservoir in monocytes/macrophages and enhanced immune protection against SARS-CoV-2. Nuclear ACE2 may represent a therapeutic target independent of the variant and strain of viruses that use the ACE2 receptor for host cell entry.

The HAP clade, mainly including Helichrysum Mill, Anaphalis DC., and Pseudognaphalium Kirp., is a major component of tribe Gnaphalieae (Asteraceae). In this clade, Anaphalis represents the largest genus of Asian Gnaphalieae. The intergeneric relationships among Anaphalis and its related genera and the infrageneric taxonomy of this genus are complex and remain controversial. However, there are few studies that have focused on these issues. Herein, based on the current most comprehensive sampling of the HAP clade, especially Anaphalis, we conducted phylogenetic analyses using chloroplast (cp) genome and nuclear ribosomal DNA (nrDNA) to evaluate the relationships within HAP clade, test the monophyly of Anaphalis, and examine the infrageneric taxonomy of this genus. Meanwhile, the morphological characters were verified to determine the circumscription and infrageneric taxonomy system of Anaphalis. Additionally, the biogeographical history, diversification processes, and evolution of crucial morphological characters were estimated and inferred. Our phylogenetic analyses suggested that Anaphalis is polyphyletic because it nested with Helichrysum and Pseudognaphalium. Two and four main clades of Anaphalis were identified in cp genome and nrDNA trees, respectively. Compared with nrDNA trees, the cp genome trees were more effective for phylogenetic resolution. After comprehensively analyzing morphological and phylogenetic evidence, it was concluded that the achene surface ornamentation and leaf base showed less homoplasy and supported the two Anaphalis lineages that were inferred from cp genome. Our biogeographical analyses based on cp genome indicated that HAP clade underwent rapid diversification from late Miocene to Pliocene. The two Anaphalis lineages appeared to have originated in Africa, then spread to Western and Southern Asia, and subsequently moved into Southwestern China forming a diversity center. The dispersal patterns of the two Anaphalis lineages were different. One dispersed around the world, except in Africa and South America. The other one dispersed to Eastern and Southeastern Asia from the ancestral origin region.

Introduction In view of the opioid epidemic and increasing caution surrounding prescription of opioids, addressing the competence of opioid management is important. There is minimal structured opioid education in Singapore. Online opioid education modules are available but lack real-time input, concise objectives, and program evaluation. This pilot online, modular, blended program aimed to efficiently instruct novice doctors on safe and appropriate practical opioid prescribing, optimizing its role in multimodal pain management while minimizing risks to patients and public health. Methods The Analysis, Design, Development, Implementation, and Evaluation (ADDIE) model was used. A multidisciplinary team developed the interactive blended program, “Comprehensive Opioid Management in Pain (COMP)”, consisting of three online modules, one case-based discussion (CBD) session, pre- and post-program evaluations. The program was designed to be concise, clinically relevant and engaging to maximize application of knowledge in clinically deficient areas. All junior anesthetists across Singhealth were invited to participate. We analyzed all self-reported and objective scores, as well as program feedback. Results 33 participants completed the online modules. Despite the moderate to high level of baseline self-reported confidence and competency scores, median scores for all variables increased post-program from pre-program. There was unanimous agreement on the relevance and utility of the training program. Conclusion This pilot achieved the aims of improving the knowledge and confidence levels of opioid management in novice doctors. Participants particularly enjoyed the succinct and interactive features of COMP. Further extension with modules focusing on opioid diversion and its use in high-risk populations would benefit intermediate learners.

Chronic hepatitis B virus (HBV) infection remains one of the major global public health concerns, and it develop into liver fibrosis, cirrhosis, and hepatocellular carcinoma. Recent evidence suggests that endosomal and autophagic vesicles are beneficial for HBV replication. However, it has not been well elucidated how HBV exploits such intracellular vesicle systems for its replication. RAB5A, a member of small GTPase family, plays crucial roles in early endosome biogenesis and autophagy initiation. We observed that RAB5A mRNA and protein levels were significantly increased in HBV-expressing hepatoma cell lines as well as in liver tissue samples from chronic HBV-infected patients. Moreover, RAB5A silencing inhibited HBV replication and subviral particle (SVP) expression significantly in HBV-transfected and -infected hepatoma cells, whereas RAB5A overexpression increased them. Mechanistically, RAB5A increases HBV replication through enhancement of early endosome (EE) – late endosome (LE) activation by interacting with EEA1, as well as enhancing autophagy induction by interacting with VPS34. Additionally, HBV infection enhances RAB5A-mediated dual activation of EE-LE system and autophagy. Collectively, our findings highlight that HBV utilizes RAB5A-mediated dual activation of endosomal and autophagic vesicle pathways for its own replication and persistence. Therefore, RAB5A is a potential target for chronic HBV infection treatment.

Abstract The plastic deformation of crystalline materials can be understood by considering their structural defects such as disclinations and dislocations. Although also glasses are solids, their structure resembles closely the one of a liquid and hence the concept of structural defects becomes ill-defined. As a consequence it is very challenging to rationalize on a microscopic level the mechanical properties of glasses close to the yielding point and to relate plastic events to structural properties. Here we investigate the topological characteristics of the eigenvector field of the vibrational excitations of a two-dimensional glass model, notably the geometric arrangement of the topological defects as a function of vibrational frequency. We find that if the system is subjected to a quasistatic shear, the location of the resulting plastic events correlate strongly with the topological defects that have a negative charge. Our results provide thus a direct link between the structure of glasses prior their deformation and the plastic events during deformation.

Abstract Background The development and innovation of biomechanical measurement methods provide a solution to the problems in ski jumping research. At present, research on ski jumping mostly focuses on the local technical characteristics of different phases, but studies on the technology transition process are less. Objectives This study aims to evaluate a measurement system (i.e. the merging of 2D video recording, inertial measurement unit and wireless pressure insole) that can capture a wide range of sport performance and focus on the key transition technical characteristics. Methods The application validity of the Xsens motion capture system in ski jumping was verified under field conditions by comparing the lower limb joint angles of eight professional ski jumpers during the takeoff phase collected by different motion capture systems (Xsens and Simi high-speed camera). Subsequently, the key transition technical characteristics of eight ski jumpers were captured on the basis of the aforementioned measurement system. Results Validation results indicated that the joint angle point-by-point curve during the takeoff phase was highly correlated and had excellent agreement (0.966 ≤ r ≤ 0.998, P

Background Methamphetamine (METH) addiction causes a huge burden on society. The prefrontal cortex (PFC), associated with emotion and cognitive behaviours, is also involved in addiction neurocircuitry. Although bulk RNA sequencing has shown METH-induced gene alterations in the mouse PFC, the impact on different cell types remains unknown.Aims To clarify the effects of METH treatment on different cell types of the PFC and the potential pathways involved in METH-related disorders.Methods We performed single-nucleus RNA sequencing (snRNA-seq) to examine the transcriptomes of 20 465 nuclei isolated from the PFC of chronic METH-treated and control mice. Main cell types and differentially expressed genes (DEGs) were identified and confirmed by RNA fluorescence in situ hybridization(FISH).Results Six main cell types were identified depending on the single-cell nucleus sequencing; of particular interest were the mature oligodendrocytes in the PFC. The DEGs of mature oligodendrocytes were enriched in the myelin sheath, adenosine triphosphate (ATP) metabolic process, mitochondrial function and components, and so on. The messenger RNA levels of Aldoc and Atp5l (FISH) and the protein level of the mitochondrial membrane pore subunit TOM40 (immunofluorescence) decreased in the mature oligodendrocytes. Fast blue staining and transmission electron microscopy image indicated myelin damage, and the myelin thickness decreased in METH brains.Conclusions snRNA-seq reveals altered transcriptomes of different cell types in mouse PFC induced by chronic METH treatment, underscoring potential relationships with psychiatric disorders.

Electroencephalography (EEG) functional connectivity (EFC) and eye tracking (ET) have been explored as objective screening methods for autism spectrum disorder (ASD), but no study has yet evaluated restricted and repetitive behavior (RRBs) simultaneously to infer early ASD diagnosis. Typically developing (TD) children (n = 27) and ASD (n = 32), age- and sex-matched, were evaluated with EFC and ET simultaneously, using the restricted interest stimulus paradigm. Network-based machine learning prediction (NBS-predict) was used to identify ASD. Correlations between EFC, ET, and Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) were performed. The Area Under the Curve (AUC) of receiver-operating characteristics (ROC) was measured to evaluate the predictive performance. Under high restrictive interest stimuli (HRIS), ASD children have significantly higher α band connectivity and significantly more total fixation time (TFT)/pupil enlargement of ET relative to TD children (p = 0.04299). These biomarkers were not only significantly positively correlated with each other (R = 0.716, p = 8.26e−4), but also with ADOS total scores (R = 0.749, p = 34e-4) and RRBs sub-score (R = 0.770, p = 1.87e-4) for EFC (R = 0.641, p = 0.0148) for TFT. The accuracy of NBS-predict in identifying ASD was 63.4%. ROC curve demonstrated TFT with 91 and 90% sensitivity, and 78.7% and 77.4% specificity for ADOS total and RRB sub-scores, respectively. Simultaneous EFC and ET evaluation in ASD is highly correlated with RRB symptoms measured by ADOS-2. NBS-predict of EFC offered a direct prediction of ASD. The use of both EFC and ET improve early ASD diagnosis.

This study is aimed to explore the feasibility of ultrasound on enhancing the fermentation properties of ginkgo kernel juice by Lactiplantibacillus plantarum Y2. Specifically, ultrasound at 20 kHz and different intensities (mild ultrasound intensity-84.42 W/L, moderate ultrasound intensity-115.50 W/L, high ultrasound intensity-173.88 W/L) with a pulse mode were applied to facilitate the fermentation process. The number of viable cells of Lactiplantibacillus plantarum Y2 increased by 5.06, 5.05 and 2.19% in the sonicated groups at 173.88, 115.50 and 84.42 W/L, compared with the non-sonicated juice after 24-h fermentation. Furthermore, mild intensity ultrasonication improved the permeability of the cell membrane, which is beneficial for the metabolism of phenolics, amino acids and organic acids. Ultrasonication increased in-vitro antioxidant activity of fermented ginkgo kernel juice by promoting the metabolism of phenolic acids, such as ferulic acid, chlorogenic and caffeic acids. At the end of fermentation, the sonicated group at 84.42 W/L has the maximum consumptions of total sugars and proteins (increased by 12.52 and 18.73%). Moreover, the reduction rate of the poison material 4′-O-methylpyridoxine (MPN) in ginkgo kernel juice increased by more than 16.40% with ultrasound treatment at 173.88 W/L after the fermentation for 48 h. Overall, ultrasound can improve the metabolizations of Lactobacillus plantarum and reduce the toxic substances, which promoted the nutritional value and flavors of ginkgo kernel juice.

Colocalization analysis of genomic region sets has been widely adopted to unveil potential functional interactions between corresponding biological attributes, which often serves as the basis for further investigation. A number of methods have been developed for colocalization analysis of genomic elements. However, none of them explicitly considered the transcriptome heterogeneity and isoform ambiguity, making them less appropriate for analyzing transcriptome elements. Here, we developed RgnTX, an R/Bioconductor tool for the colocalization analysis of transcriptome elements with permutation tests. Different from existing approaches, RgnTX directly takes advantage of transcriptome annotation, and offers high flexibility in the null model to simulate realistic transcriptome-wide background, such as the complex alternative splicing patterns. Importantly, it supports the testing of transcriptome elements without clear isoform association, which is often the real scenario due to technical limitations. Proposed package offers a wide selection of pre-defined functions, easy to be utilized by users for visualizing permutation results, calculating shifted z-scores and conducting multiple hypothesis testing under Benjamini-Hochberg correction. Moreover, with synthetic and real datasets, we show that RgnTX novel testing modes return distinct and more significant results compared to existing genome-based methods. We believe RgnTX should make a useful tool to characterize the randomness of the transcriptome, and for conducting statistical association analysis for genomic region sets within the heterogeneous transcriptome. The package now has been accepted by Bioconductor and is freely available at: https://bioconductor.org/packages/RgnTX.

Abstract As an indispensable enzyme for the hydrolysis of dextran, dextranase has been widely used in the fields of food and medicine. It should be noted that the weak thermostability of dextranase has become a restricted factor for industrial applications. This study aims to improve the thermostability of dextranase AoDex in glycoside hydrolase (GH) family 49 that derived from Arthrobacter oxydans KQ11. Some mutants were predicted and constructed based on B-factor analysis, PoPMuSiC and HotMuSiC algorithms, and four mutants exhibited higher heat resistance. Compared with the wild-type, mutant S357P showed the best improved thermostability with a 5.4-fold increase of half-life at 60 °C, and a 2.1-fold increase of half-life at 65 °C. Furthermore, S357V displayed the most obvious increase in enzymatic activity and thermostability simultaneously. Structural modeling analysis indicated that the improved thermostability of mutants might be attributed to the introduction of proline and hydrophobic effects, which generated the rigid optimization of the structural conformation. These results illustrated that it was effective to improve the thermostability of dextranase AoDex by rational design and site-directed mutagenesis. The thermostable mutant of dextranase AoDex has potential application value, and it can also provide references for engineering other thermostable dextranases of the GH49 family.

Purpose The purpose of this study was to investigate the prevalence and risk factors of overactive bladder (OAB) in young adults and to explore the influence of OAB on mental health. Methods Between October 2019 and January 2020, 14,010 anonymous questionnaires were distributed to freshmen at 2 universities in Henan, China. The students came from all over the country. The questionnaire included general items and information necessary to calculate the overactive bladder symptom score, the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) score, Self-Esteem Scale (SES) score, and Self-Rating Depression Scale (SDS) score. The relationships between the prevalence of OAB and its risk factors were evaluated. Results The overall prevalence of OAB was 6.0%, with 4.3% of participants characterized as having dry OAB and 1.7% as having wet OAB. The prevalence of mild OAB was 5.5%, and that of moderate OAB was 0.5%; no severe OAB was observed. Higher prevalence rates of OAB were found among women, respondents with constipation, and respondents with primary nocturnal enuresis (PNE) (P

DNA methylation is one of the earliest epigenetic regulation mechanisms studied extensively, and it is critical for normal development, diseases, and gene expression. As a recently identified chemical modification of DNA, N4-acetyldeoxycytosine (4acC) was shown to be abundant in Arabidopsis and highly associated with gene expression and actively transcribed genes. Precise identification of 4acC is essential for studying its biological function. We proposed the 4acCPred, the first computational framework for predicting 4acC-carrying regions from Arabidopsis genomic DNA sequences. Since the existing 4acC data are not precise for a specific base but only report regions that are hundreds of bases long, we formulated the task as a weakly supervised learning problem and built 4acCPred using a multi-instance-based deep neural network. Both cross-validation and independent testing on the four datasets under different conditions show promising performance, with mean areas under the receiver operating characteristic curve (AUCs) of 0.9877 and 0.9899, respectively. 4acCPred also provides motif mining through model interpretation. The motifs found by 4acCPred are consistent with existing knowledge, indicating that the model successfully captured real biological signals. In addition, a user-friendly web server was built to facilitate 4acC prediction, motif visualization, and data access. Our framework and web server should serve as useful tools for 4acC research.

Gastrointestinal (GI) disorders are common comorbidities in individuals with autism spectrum disorder (ASD), and abnormalities in these issues have been found to be closely related to the severity of core behavioral deficits in autism. The enteric nervous system (ENS) plays a crucial role in regulating various aspects of gut functions, including gastrointestinal motility. Dysfunctional wiring in the ENS not only results in various gastrointestinal issues, but also correlates with an increasing number of central nervous system (CNS) disorders, such as ASD. However, it remains unclear whether the gastrointestinal dysfunctions are a consequence of ASD or if they directly contribute to its pathogenesis. This review focuses on the deficits in the ENS associated with ASD, and highlights several high-risk genes for ASD, which are expressed widely in the gut and implicated in gastrointestinal dysfunction among both animal models and human patients with ASD. Furthermore, we provide a brief overview of environmental factors associated with gastrointestinal tract in individuals with autism. This could offer fresh perspectives on our understanding of ASD.

Background Combination therapy with radioembolization (yttrium-90)-resin microspheres) followed by nivolumab has shown a promising response rate of 30.6% in a Phase II trial (CA209-678) for advanced hepatocellular carcinoma (HCC); however, the response mechanisms and relevant biomarkers remain unknown.Methods By collecting both pretreatment and on-treatment samples, we performed multimodal profiling of tissue and blood samples and investigated molecular changes associated with favorable responses in 33 patients from the trial.Results We found that higher tumor mutation burden, NCOR1 mutations and higher expression of interferon gamma pathways occurred more frequently in responders. Meanwhile, non-responders tended to be enriched for a novel Asian-specific transcriptomic subtype (Kaya_P2) with a high frequency of chromosome 16 deletions and upregulated cell cycle pathways. Strikingly, unlike other cancer types, we did not observe any association between T-cell populations and treatment response, but tumors from responders had a higher proportion of CXCL9+/CXCR3+ macrophages. Moreover, biomarkers discovered in previous immunotherapy trials were not predictive in the current cohort, suggesting a distinctive molecular landscape associated with differential responses to the combination therapy.Conclusions This study unraveled extensive molecular changes underlying distinctive responses to the novel treatment and pinpointed new directions for harnessing combination therapy in patients with advanced HCC.

The infrageneric taxonomy system, species delimitation, and interspecies systematic relationships of Leontopodium remain controversial and complex. However, only a few studies have focused on the molecular phylogeny of this genus. In this study, the characteristics of 43 chloroplast genomes of Leontopodium and its closely related genera were analyzed. Phylogenetic relationships were inferred based on chloroplast genomes and nuclear ribosomal DNA (nrDNA). Finally, together with the morphological characteristics, the relationships within Leontopodium were identified and discussed. The results showed that the chloroplast genomes of Filago, Gamochaeta, and Leontopodium were well-conserved in terms of gene number, gene order, and GC content. The most remarkable differences among the three genera were the length of the complete chloroplast genome, large single-copy region, small single-copy region, and inverted repeat region. In addition, the chloroplast genome structure of Leontopodium exhibited high consistency and was obviously different from that of Filago and Gamochaeta in some regions, such as matk, trnK (UUU)-rps16, petN-psbM, and trnE (UUC)-rpoB. All the phylogenetic trees indicated that Leontopodium was monophyletic. Except for the subgeneric level, our molecular phylogenetic results were inconsistent with the previous taxonomic system, which was based on morphological characteristics. Nevertheless, we found that the characteristics of the leaf base, stem types, and carpopodium base were phylogenetically correlated and may have potential value in the taxonomic study of Leontopodium. In the phylogenetic trees inferred using complete chloroplast genomes, the subgen. Leontopodium was divided into two clades (Clades 1 and 2), with most species in Clade 1 having herbaceous stems, amplexicaul, or sheathed leaves, and constricted carpopodium; most species in Clade 2 had woody stems, not amplexicaul and sheathed leaves, and not constricted carpopodium.

Objectives Medical errors (MEs) and adverse events (AEs) both had long-term impacts on healthcare professionals. Studies investigated the associations between MEs, AEs, psychological distress and suicidal behaviours among healthcare professionals. The aim of the current study was to explore the mediating role of psychological distress in the relationship between MEs/AEs and suicidal ideation/suicide plan among operating room nurses in China.Design A cross-sectional study.Setting The survey was conducted between December 2021 and January 2022 in China.Participants A total of 787 operating room nurses completed the questionnaires in China.Primary and secondary outcome measures The primary outcome measures were MEs and AEs. Secondary outcome measures were psychological distress and suicidal behaviours.Results The results showed that 22.1% of operating room nurses were involved in MEs, while 13.9% of operating room nurses were involved in AEs. The associations between suicidal ideation (OR=1.10, p

BackgroundEvidence suggests that there is a robust relationship between altered neuroanatomy and autistic symptoms in individuals with autism spectrum disorder (ASD). Social visual preference, which is regulated by specific brain regions, is also related to symptom severity. However, there were a few studies explored the potential relationships among brain structure, symptom severity, and social visual preference.MethodsThe current study investigated relationships among brain structure, social visual preference, and symptom severity in 43 children with ASD and 26 typically developing (TD) children (aged 2–6 years).ResultsSignificant differences were found in social visual preference and cortical morphometry between the two groups. Decreased percentage of fixation time in digital social images (%DSI) was negatively related to not only the thickness of the left fusiform gyrus (FG) and right insula, but also the Calibrated Severity Scores for the Autism Diagnostic Observation Schedule-Social Affect (ADOS-SA-CSS). Mediation analysis showed that %DSI partially mediated the relationship between neuroanatomical alterations (specifically, thickness of the left FG and right insula) and symptom severity.ConclusionThese findings offer initial evidence that atypical neuroanatomical alterations may not only result in direct effects on symptom severity but also lead to indirect effects on symptom severity through social visual preference. This finding enhances our understanding of the multiple neural mechanisms implicated in ASD.

Abstract Normal Tau promotes the assembly and stabilization of microtubules, thus, maintaining axon transport. In Alzheimer’s disease (AD), Tau aggregation causes it to lose these above-mentioned functions. However, the molecular mechanism leading to Tau aggregation in AD remains ambiguous. Here, we report that USP10, one of the important deubiquitinases (DUBs), is involved in Tau aggregation. We found that USP10 is upregulated in postmortem human AD and APP/PS1 mice brains, but not in P301S mice brains. Moreover, in primary neuronal cultures, Aβ42 induces a dose-dependent USP10 upregulation, an increase in the levels of both total and phosphorylated Tau, as well as a markedly elevated Tau binding with USP10, that is accompanied by a significantly decreased Tau ubiquitination. In addition, overexpression of USP10 directly causes an increase in the levels of total and phosphorylated Tau, induces Tau aggregation, and delays in Tau degradation. Results from mass spectrometry, reciprocal immunoprecipitation, and immunofluorescence assays strongly prove Tau’s interaction with USP10. This is further supported by the Tau307–326K and Tau341–378K peptides’ competitive inhibition of Tau binding with USP10, attenuating Tau hyperphosphorylation and Tau deubiquitination. Together, our data strongly indicate that USP10 plays a critical role in mediating Tau aggregation via downregulating its ubiquitination and thus slowing down Tau turnover. Inhibition of USP10-Tau interaction might be therapeutically useful in the management of AD and related tauopathies.

Abstract To explore the dynamic mechanical characteristics of CRCB specimens, a separated Hopkinson pressure bar (SHPB) test device combined with ultra-high-speed camera system was used to carry out the impact compression test on CRCB specimens. The stress wave propagation, dynamic stress–strain relationship, dynamic evolution of cracks, energy dissipation law and failure characteristics of the coal–rock combined body in the case of stress waves entering coal from rock were compared and analyzed. The influence of the difference between the rock and the incident bar on the propagation of stress wave gradually weakens with the increase of the impact velocity. The strength stress and peak strain of the CRCB specimens have obvious strain-rate effects. Besides, with increased impact velocity, the incident energy increases linearly, the reflected energy proportion decreases linearly and the absorbed energy proportion change approximately as a power function. Under the same stress wave, as the strength of the rock increases, the failure degree of coal gradually increases, the broken particles gradually transition from massive to powder and the rock mode changes from splitting failure to shear failure. As a result, the average particle size of broken coal blocks decreases, and the fractal dimension of CRCB specimens increases gradually. The research results provide basic research for the control of surrounding rock of roadway under dynamic pressure.

How to effectively extract electrons from subsurface oxygen defects is challenging in heterogeneous catalysis. Here the authors demonstrate that Metallic In-embedded In2O3 nanoflake catalyst promotes the delocalization of electrons among subsurface oxygen defects, obviously increasing electron density of surface active sites.

The preparation of slurry from multi-source solid waste for underground backfill adds a way out for solid waste disposal, which is beneficial to reduce environmental impact. In this paper, the effects of gangue, fly ash, gasification coarse slag and desulfurization gypsum on the fluidity, early strength, thermal stability and other properties of the backfill slurry were studied by fluidity test, strength test, Thermo-Gravimetric Analysis (TGA), Scanning Electron Microscope (SEM) and X-ray Diffraction (XRD). The results show that: (1) When G/SW (mass ratio of gangue to solid waste)