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Abstract This single-arm phase II non-randomised trial (ACTRN12619001265167) evaluated trastuzumab emtansine in solid cancers with HER2 amplification or mutation detected by comprehensive genomic profiling. The primary objective was objective response (OR), while secondary objectives included the time to progression (TTP) on study to TTP on prior therapy ratio, progression-free survival (PFS) and overall survival (OS). The cohort included 16 tumours with HER2 mutations (group 1) and 16 with HER2 amplification (group 2). After 17 months median follow-up, ORs occurred in 19% of group 1 (1 salivary gland carcinoma (SGC), 2 lung cancers) and 25% of group 2 (3 SGCs, 1 uterine carcinoma). Fourteen of 29 TTP-evaluable patients achieved a TTP ratio ≥1.3, including 10 without an OR. Median PFS and OS were 4.5 (95% CI 2.1–7.0) and 18.2 months (95% CI 8.1-not reached) respectively. Trastuzumab emtansine showed modest ORs and a favourable change in disease trajectory in select HER2-altered solid cancers.

Abstract Background Liver cancer (LC) screening, such as AFP test and abdominal ultrasound, is an effective way to prevent LC, one of the most common cancers worldwide. Despite the proven screening benefits, screening participation among high-risk populations for LC remains low. This suggests that targeted, systematic, and effective interventions should be provided to improve knowledge and awareness related to LC screening, enhance screening intentions, and thereby promote screening behaviors. Telephone is people’s main medium of daily communication and mHealth-based programs offer a potential and effective solution for promoting health behaviors. The purpose of this study is to develop and implement a mHealth (WeChat app) based intervention guided by Fogg’s Behavior Model (FBM) to augment the knowledge of LC prevention among people at risk of LC and enhance their motivation for screening, and to validate its effectiveness in improving LC screening. Methods We propose a two-arm, single-blind randomized controlled trial with 82 at-risk individuals of LC, delivering a 6-month mHealth-based intervention program with optional health counseling. Recruitment will be through tertiary hospitals and community organizations in 4 districts in Heng Yang. In total, 82 individuals at high risk for HCC will be randomized 1:1 to intervention or control (usual care) groups. The intervention group will receive intervention, whose contents are based on the FBM model, via multiple forms of media including PowerPoint presentation, multimedia video, health information booklet and screening message, which is delivered in the WeChat Applet. Control dyads will be provided with usual health education. Outcomes will be assessed at baseline and post-intervention. Discussion The findings of this study will provide evidence of the benefits of utilizing mHealth-based approaches in intervention development to enhance the effectiveness of screening adherence for high-risk people of LC. Further, the findings would provide reference to the potential incorporation of the targeted intervention in local community organizations. Trial registration Chinese Clinical Trial Registry (ChiCTR2400080530) Date registered: 31/1/2024.

Abstract Background This study evaluates a three-dimensional (3D) visualisation design combined with customized surgical guides to assist anterior maxillary segmental distraction osteogenesis (AMSDO) in correcting maxillary hypoplasia in adolescents with cleft lip and palate (CLP), focusing on treatment outcomes, satisfaction and the validity of 3D planning. Methods This retrospective cohort study was conducted at a single hospital in China. Between January 2020 and December 2023, 12 adolescents with CLP with maxillary hypoplasia were included. An advanced 3D simulation was used to convey the treatment strategy to the patients and their families. A customized surgical guide and distraction osteogenesis device were designed. Cephalometric analysis evaluated AMSDO changes and long-term stability. Patient satisfaction was assessed. The Chinese version of the Child Oral Health Impact Profile was used to evaluate the children’s oral health-related quality of life before and after treatment. The postoperative outcomes were compared with the planned outcomes by superimposing the actual postoperative data onto the simulated soft tissue models and calculating the linear and angular differences between them. Results One patient experienced postoperative gingivitis, yielding an 8.33% complication rate. Most patients (83.33%) were highly satisfied with the target position, with the rest content. Cephalometric analysis showed significant improvements in various indices post-traction. Quality-of-life scores significantly improved post-treatment. The discrepancies in facial soft tissue between the simulated and actual results were within clinically satisfactory ranges. Conclusions Digitally designed surgical guides effectively treat maxillary hypoplasia in adolescents with CLP, ensuring stability, reducing complications, reducing dependency on operator experience, and enhancing satisfaction and health outcomes. Although the simulated results were clinically acceptable, it is important to inform patients of potential variations in the predicted soft tissue.

Abstract Objective This study aimed to identify a quantitative index for optical coherence tomography (OCT) images to discriminate tumours from surrounding tissues. Subjects and methods Based on OCT measurements, mean grey values were determined from 432 locations on fifty-four human tissue specimens (eighteen cancerous, para-cancerous, and normal tissues each). These results were histologically evaluated by hematoxylin and eosin staining (H&E). Results The mean grey values of oral squamous cell carcinoma (OSCC) measurements were significantly different from those of the surrounding healthy tissue (p value

Abstract Sleep disturbances, including rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness, and insomnia, are common non-motor manifestations of Parkinson’s disease (PD). Little is known about the underlying mechanisms, partly due to the inability of current rodent models to adequately mimic the human PD sleep phenotype. Clinically, increasing studies have reported that variants of the glucocerebrosidase gene (GBA) increase the risk of PD. Here, we developed a mouse model characterized by sleep–wakefulness by injecting α-synuclein preformed fibronectin (PFF) into the sublaterodorsal tegmental nucleus (SLD) of GBA L444P mutant mice and investigated the role of the GBA L444P variant in the transition from rapid eye movement sleep behavior disorder to PD. Initially, we analyzed spectral correlates of REM and NREM sleep in GBA L444P mutant mice. Importantly, EEG power spectral analysis revealed that GBA L444P mutation mice exhibited reduced delta power during non-rapid eye movement (NREM) sleep and increased theta power (8.2–10 Hz) in active rapid eye movement (REM) sleep phases. Our study revealed that GBA L444P-mutant mice, after receiving PFF injections, exhibited increased sleep fragmentation, significant motor and cognitive dysfunctions, and loss of dopaminergic neurons in the substantia nigra. Furthermore, the over-expression of GBA-AAV partially improved these sleep disturbances and motor and cognitive impairments. In conclusion, we present the initial evidence that the GBA L444P mutant mouse serves as an essential tool in understanding the complex sleep disturbances associated with PD. This model further provides insights into potential therapeutic approaches, particularly concerning α-synuclein accumulation and its subsequent pathological consequences.

Abstract Background Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system. Methods The levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB −/− mice were generated, and relevant in vivo experiments were performed. Results Here, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB −/− mice exhibited resistance to ANGPTL8-induced neuroinflammation and synaptic damage. Conclusion Taken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.

Introduction: Peanut is susceptible to infection of Aspergillus fungi and conducive to aflatoxin contamination, hence developing aflatoxin-resistant variety is highly meaningful. Identifying functional genes or loci conferring aflatoxin resistance and molecular diagnostic marker are crucial for peanut breeding. Objectives: This work aims to (1) identify candidate gene for aflatoxin production resistance, (2) reveal the related resistance mechanism, and (3) develop diagnostic marker for resistance breeding program. Methods: Resistance to aflatoxin production in a recombined inbred line (RIL) population derived from a high-yielding variety Xuhua13 crossed with an aflatoxin-resistant genotype Zhonghua 6 was evaluated under artificial inoculation for three consecutive years. Both genetic linkage analysis and QTL-seq were conducted for QTL mapping. The candidate gene was further fine-mapped using a secondary segregation mapping population and validated by transgenic experiments. RNA-Seq analysis among resistant and susceptible RILs was used to reveal the resistance pathway for the candidate genes. Results: The major effect QTL qAFTRA07.1 for aflatoxin production resistance was mapped to a 1.98 Mbp interval. A gene, AhAftr1 (Arachis hypogaea Aflatoxin resistance 1), was detected structure variation (SV) in leucine rich repeat (LRR) domain of its production, and involved in disease resistance response through the effector-triggered immunity (ETI) pathway. Transgenic plants with overexpression of AhAftr1(ZH6) exhibited 57.3% aflatoxin reduction compared to that of AhAftr1(XH13). A molecular diagnostic marker AFTR.Del.A07 was developed based on the SV. Thirty-six lines, with aflatoxin content decrease by over 77.67% compared to the susceptible control Zhonghua12 (ZH12), were identified from a panel of peanut germplasm accessions and breeding lines through using AFTR.Del.A07. Conclusion: Our findings would provide insights of aflatoxin production resistance mechanisms and laid meaningful foundation for further breeding programs.

Abstract Different delivery methods can cause variations in the composition and structure of intestinal microbiota in neonates. However, the impact of the microecological environment on host immune function requires further investigation. In this study, 75 healthy neonates were divided into two groups: vaginal delivery group (n = 36) and cesarean section group (n = 39). Fecal and peripheral blood samples were collected from the 7th to the 10th day. 16S rRNA sequencing technique was performed to investigate the gut microbiota on fecal samples. Levels of immunoglobulins and Th1 and Th2 cells in the peripheral blood of neonates were measured. The abundance of Escherichia, Bifidobacterium, and Bacteroides in neonates in the cesarean section group was significantly lower than that in the vaginal delivery group. Metabolic pathway analysis showed three significantly up-regulated metabolic pathways in the intestinal microbiota of neonates in the cesarean section group. The levels of serum IgG and IL-12p70 in the cesarean section group were lower than those in the vaginal delivery group, and the proportion of IFN-γ/IL-4 was significantly lower in the cesarean section group compared to the vaginal delivery group. The mode of delivery has potential impact on the intestinal microbiota and immune functions of neonates, potentially leading to an imbalance of Th1/Th2 cells in neonates delivered by cesarean section.

Abstract We study quantum steering and Bell nonlocality harvested by the local interaction of two Unruh-DeWitt detectors with the vacuum massless scalar field, both in the presence of gravitational waves and in Minkowski spacetime. It is shown that quantum steerability under the influence of gravitational waves can be greater than or less than quantum steerability in Minkowski spacetime, which means that the gravitational waves can amplify or degrade the harvested steering. In particular, a resonance effect occurs when the energy gap of the detector is tuned to the frequency of the gravitational wave. We also find that the harvesting-achievable separation range of vacuum steering can be expanded or reduced by the presence of gravitational waves, which depends on the energy gap, the gravitational wave frequency, and the duration of the gravitational wave action. It is interesting to note that two detector systems that satisfy the Bell inequality in most parameter spaces, regardless of the existence of gravitational waves, indicating that steering harvesting cannot be considered to be nonlocal.

Abstract Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal–amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.

Abstract Background The acute and long-term benefits of exercise training on cardiovascular health have been well established. The systematic review and meta-analysis aimed to systematically assess the effectiveness of exercise training on arterial stiffness and blood pressure among postmenopausal women with elevated blood pressure. Methods A comprehensive search was conducted on PubMed, Embase, Web of Science, ProQuest, Cochrane Library, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov website from inception to September 30, 2023, to identify the randomized controlled trials (RCTs), which evaluated the effectiveness of exercise training on arterial stiffness and blood pressure in postmenopausal women. Standardized mean differences (SMD), weighted mean differences (WMD), and 95% confidence intervals (95% CIs) were calculated using random/fixed effects models. Quality assessment was performed using the modified Jadad scale and the Cochrane Risk of Bias Tool. Sensitivity analysis and subgroup analysis were conducted based on drug dosage, treatment duration, and age of administration to further explore potential heterogeneity. Funnel plots were performed to assess publication bias and Begg’s regression test was carried out for funnel plot asymmetry. Results Twenty-two RCTs involving 1978 participants were included in the quantitative analysis. The mean quality of eligible studies was 4.2 out of 7 based on the modified Jadad scale. The results indicated that exercise training had a significant effect on reducing brachial-ankle pulse wave velocity [MD = − 0.69, 95%CI (− 1.11, − 0.27), P = 0.001], decreasing augmentation index (AIx) [MD = − 6.00, 95%CI (− 6.39, − 5.61), P

Background: When resuscitating patients with septic shock, cerebrovascular reactivity parameters are calculated by monitoring regional cerebral oxygen saturation (rSO2) using near-infrared spectroscopy to determine the optimal blood pressure. Here, we aimed to analyze the impact of cerebral autoregulation-directed optimal blood pressure management on the incidence of delirium and the prognosis of patients with septic shock. Methods: This prospective randomized controlled clinical study was conducted in the Xiangya Hospital of Central South University, China. Fifty-one patients with septic shock (December 2020–May 2022) were enrolled and randomly allocated to the experimental (n=26) or control group (n=25). Using the ICM+ software, we monitored the dynamic changes in rSO2 and mean arterial pressure (MAP) and calculated the cerebrovascular reactivity parameter tissue oxygen reactivity index to determine the optimal blood pressure to maintain normal cerebral autoregulation function during resuscitation in the experimental group. The control group was treated according to the Surviving Sepsis Campaign Guidelines. Differences in the incidence of delirium and 28-day mortality between the two groups were compared, and the risk factors were analyzed. Results: The 51 patients, including 39 male and 12 female, had a mean age of (57.0±14.9) years. The incidence of delirium was 40.1% (23/51), and the 28-day mortality rate was 29.4% (15/51). The mean MAP during the first 24 h of intensive care unit (ICU) admission was higher ([84.5±12.2] mmHg vs. [77.4±11.8] mmHg, P=0.040), and the incidence of delirium was lower (30.8% vs. 60.0%, P=0.036) in the experimental group than in the control group. The use of cerebral autoregulation-directed optimal blood pressure (odds ratio [OR]=0.090, 95% confidence interval [CI]: 0.009 to 0.923, P=0.043) and length of ICU stay (OR=1.473, 95% CI: 1.093 to 1.985, P=0.011) were risk factors for delirium during septic shock. Vasoactive drug dose (OR=8.445, 95% CI: 1.26 to 56.576, P=0.028) and partial pressure of oxygen (PaO2) (OR=0.958, 95% CI: 0.921 to 0.996, P=0.032) were the risk factors for 28-day mortality. Conclusions: The use of cerebral autoregulation-directed optimal blood pressure management during shock resuscitation reduces the incidence of delirium in patients with septic shock. Trial Registration: ClinicalTrials.gov ldentifer: NCT03879317

Background/purpose: Clear aligners are popular orthodontic tools because of their relatively aesthetic appearance and convenience of use. Nevertheless, bodily tooth movements still present challenges. This study evaluated various configurations of attachments placed on the mandibular canine in terms of the efficiency of canine bodily movement and correction of tipping. Materials and methods: A finite element model of the mandible was constructed to investigate the effects of various attachment configurations on the overall bodily movement and undesirable tipping of a mandibular canine. Canine movements were categorized into four types, namely tipping and bodily movements in the mesial and distal directions. The size and shape of the attachments were fixed, but their placement and orientation were varied. Five and seven attachment configurations were evaluated for their influence on tipping and bodily movements, respectively. Results: Attachment configuration significantly influenced mandibular canine tipping. The mesial occlusal–distal cervical and mesial occlusal–mesial cervical configurations had notable effects on mesial tipping, and the mesial occlusal–mesial cervical configuration excelled in distal tipping by increasing strain by 33.1%. The mesial occlusal–mesial cervical attachment configuration consistently had superior efficiency in facilitating both mesial and distal bodily movements of the canine. Conclusion: The mesial occlusal–mesial cervical attachment configuration excelled in all four types of canine movement. Irrespective of the attachment configuration, canines tend to move overall with slight tipping due to skeletal resistance and their center of rotation. The attachment configuration is crucial to the success of clear aligner treatment and must be carefully considered in clinical practice.

Background/purpose: The aim of this study was to determine the effects of age and sex on the difference between chronological age (CA) and dental age (DA) predicted using the Demirjian and Willems methods in Taiwanese children. Materials and methods: A total of 232 periapical X-ray images were obtained from children aged 5–12 years in Taiwan. Among them, 119 were boys, and 113 were girls. DA was calculated on the basis of the X-ray images of permanent teeth by using the aforementioned methods. The children were stratified by age (5–9 years [early mixed dentition period] vs. 10–12 years [late mixed dentition period]) and sex (boys vs. girls). Statistical analyses were performed to investigate potential age- and sex-based differences in the correlation between CA and DA. Results: No significant difference was observed between the mean CA and DA predicted using the Willems method in children with late mixed dentition and in girls. However, the correlation between CA and DA was stronger in children with early mixed dentition than in those with late mixed dentition and also stronger in boys than in girls. Conclusion: For children in mid-Taiwan, age and sex influence the development of permanent teeth. In addition, the correlation between DA and CA is relatively strong for boys in the early mixed dentition period.

Abstract Enhanced Recovery After Surgery (ERAS) protocols have substantially proven their merit in diminishing recuperation durations and mitigating postoperative adverse events in geriatric populations undergoing colorectal cancer procedures. Despite this, the pivotal aspect of postoperative pain control has not garnered the commensurate attention it deserves. Typically, employing a multimodal analgesia regimen that weaves together nonsteroidal anti-inflammatory drugs, opioids, local anesthetics, and nerve blocks stands paramount in curtailing surgical complications and facilitating reduced convalescence within hospital confines. Nevertheless, this integrative pain strategy is not devoid of pitfalls; the specter of organ dysfunction looms over the geriatric cohort, rooted in the abuse of analgesics or the complex interplay of polypharmacy. Revolutionary research is delving into alternative delivery and release modalities, seeking to allay the inadvertent consequences of analgesia and thereby potentially elevating postoperative outcomes for the elderly post-colorectal cancer surgery populace. This review examines the dual aspects of multimodal analgesia regimens by comparing their established benefits with potential limitations and offers insight into the evolving strategies of drug administration and release.

Autoantibodies against apolipoprotein A-I (ApoA-I) are associated with cardiovascular disease risks. We aimed to examine the 4-hydroxy-2-nonenal (HNE) modification of ApoA-I in coronary artery disease (CAD) and evaluate the potential risk of autoantibodies against their unmodified and HNE-modified peptides. We assessed plasma levels of ApoA-I, HNE-protein adducts, and autoantibodies against unmodified and HNE-peptide adducts, and significant correlations and odds ratios (ORs) were examined. Two novel CAD-specific HNE-peptide adducts, ApoA-I251–262 and ApoA-I70–83, were identified. Notably, immunoglobulin G (IgG) anti-ApoA-I251–262 HNE, IgM anti-ApoA-I70–83 HNE, IgG anti-ApoA-I251–262, IgG anti-ApoA-I70–83, and HNE-protein adducts were significantly correlated with triglycerides, creatinine, or high-density lipoprotein in CAD with various degrees of stenosis (70%). The HNE-protein adduct (OR = 2.208-fold, p = 0.020) and IgM anti-ApoA-I251–262 HNE (2.046-fold, p = 0.035) showed an increased risk of progression from >30% stenosis in CAD. HNE-protein adducts and IgM anti-ApoA-I251–262 HNE may increase the severity of CAD at high and low levels, respectively.

Abstract Background Whole plant senescence represents the final stage in the life cycle of annual plants, characterized by the decomposition of aging organs and transfer of nutrients to seeds, thereby ensuring the survival of next generation. However, the transcriptomic profile of vegetative organs during this death process remains to be fully elucidated, especially regarding the distinctions between natural programmed death and artificial sudden death induced by herbicide. Results Differential genes expression analysis using RNA-seq in leaves and roots of Arabidopsis thaliana revealed that natural senescence commenced in leaves at 45–52 days after planting, followed by roots initiated at 52–60 days. Additionally, both organs exhibited similarities with artificially induced senescence by glyphosate. Transcription factors Rap2.6L and WKRY75 appeared to serve as central mediators of regulatory changes during natural senescence, as indicated by co-expression networks. Furthermore, the upregulation of RRTF1, exclusively observed during natural death, suggested its role as a regulator of jasmonic acid and reactive oxygen species (ROS) responses, potentially triggering nitrogen recycling in leaves, such as the glutamate dehydrogenase (GDH) shunt. Root senescence was characterized by the activation of AMT2;1 and GLN1;3, facilitating ammonium availability for root-to-shoot translocation, likely under the regulation of PDF2.1. Conclusions Our study offers valuable insights into the transcriptomic interplay between phytohormones and ROS during whole plant senescence. We observed distinct regulatory networks governing nitrogen utilization in leaf and root senescence processes. Furthermore, the efficient allocation of energy from vegetative organs to seeds emerges as a critical determinant of population sustainability of annual Arabidopsis.

Abstract Recently, Zhang et al. [Eur. Phys. J. C 84, 381, https://doi.org/10.1140/epjc/s10052-024-12723-8 (2024)] constrained the Yukawa correction in the general free scalar–tensor gravity by borrowing the measured values of the parametrized post-Newtonian (PPN) parameters $$\gamma -1=(2.1\pm 2.3)\times 10^{-5}$$ γ - 1 = ( 2.1 ± 2.3 ) × 10 - 5 and $$\beta -1=(-\,4.1\pm 7.8)\times 10^{-5}$$ β - 1 = ( - 4.1 ± 7.8 ) × 10 - 5 in the Solar System tests. They firstly defined two PPN parameters $$\gamma (r)$$ γ ( r ) and $$\beta (r)$$ β ( r ) in the gravity, which depend on the radial distance r and include the Yukawa-type parameters. Then, by comparing between the experiments’ results of two PPN parameters and their $$\gamma (r)$$ γ ( r ) and $$\beta (r)$$ β ( r ) , the authors claimed that they gave the tightest bound on the gravity by the Cassini tracking experiment. However, we find their approach is not rigorous. In this paper, corresponding astronomical experiments have been physically modelled by considering the lightlike and the timelike geodesics in the general free scalar–tensor gravity. Contrary to the wrong results in Zhang et al.’s work, it is shown that the Cassini tracking experiment is insensitive to the general free scaler–tensor gravity. Furthermore, we also find that the time delay and the light deflection are all independent of the gravity. Due to an additional Yukawa-type advance in the periastron shift, we derive very much improved bounds on the Yukawa-type parameters of this gravity.

Abstract Wounding initiates intricate responses crucial for tissue repair and regeneration. Yet, the gene regulatory networks governing wound healing remain poorly understood. Here, employing single-worm RNA sequencing (swRNA-seq) across 12 time-points, we delineated a three-stage wound repair process in C. elegans: response, repair, and remodeling. Integrating diverse datasets, we constructed a dynamic regulatory network comprising 241 transcription regulators and their inferred targets. We identified potentially seven autoregulatory TFs and five cross-autoregulatory loops involving pqm-1 and jun-1. We revealed that TFs might interact with chromatin factors and form TF-TF combinatory modules via intrinsically disordered regions to enhance response robustness. We experimentally validated six regulators functioning in transcriptional and translocation-dependent manners. Notably, nhr-76, daf-16, nhr-84, and oef-1 are potentially required for efficient repair, while elt-2 may act as an inhibitor. These findings elucidate transcriptional responses and hierarchical regulatory networks during C. elegans wound repair, shedding light on mechanisms underlying tissue repair and regeneration.

Abstract Background Syntaxin6 (STX6) is a SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptors) protein complex located in the trans-Golgi network and endosomes, which is closely associated with a variety of intracellular membrane transport events. STX6 has been shown to be overexpressed in a variety of human malignant tumors such as esophageal, colorectal, and renal cell carcinomas, and participates in tumorigenesis and development. Methods Based on clinical public database and clinical liver samples analysis, the expression of STX6 in hepatocellular carcinoma (HCC) tissues was investigated. The effects of STX6 on proliferation, migration and invasion of HCC cell in vitro and in vivo were evaluated through gain- and loss-of-function studies. We further performed RNA-seq analysis and protein interactome analysis, to further decifer the detailed mechanisms of STX6 in the regulation of the JAK-STAT pathway in HCC. Results STX6 expression was upregulated in HCC tissues and its expression was highly correlated with the high histological grade of the tumor. STX6 promoted HCC cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, STX6 mediated tumor progression depending on promoting the activation of JAK-STAT signaling pathway. Receptor for activated protein kinase C (RACK1) as an essential adaptor protein mediating STX6 regulation of JAK-STAT pathway. Specifically, STX6 interacted with RACK1 and then recruited signal transducer and activator of transcription 3 (STAT3) to form a protein-binding complex and activates STAT3 transcriptional activity. Conclusions This study provided a novel concept that STX6 exerted oncogenic effects by activating the STAT3 signaling pathway, and STX6 might be a promising therapeutic target for HCC.

Abstract Anti-HSV therapies are only suppressive because they do not eliminate latent HSV present in ganglionic neurons, the source of recurrent disease. We have developed a potentially curative approach against HSV infection, based on gene editing using HSV-specific meganucleases delivered by adeno-associated virus (AAV) vectors. Gene editing performed with two anti-HSV-1 meganucleases delivered by a combination of AAV9, AAV-Dj/8, and AAV-Rh10 can eliminate 90% or more of latent HSV DNA in mouse models of orofacial infection, and up to 97% of latent HSV DNA in mouse models of genital infection. Using a pharmacological approach to reactivate latent HSV-1, we demonstrate that ganglionic viral load reduction leads to a significant decrease of viral shedding in treated female mice. While therapy is well tolerated, in some instances, we observe hepatotoxicity at high doses and subtle histological evidence of neuronal injury without observable neurological signs or deficits. Simplification of the regimen through use of a single serotype (AAV9) delivering single meganuclease targeting a duplicated region of the HSV genome, dose reduction, and use of a neuron-specific promoter each results in improved tolerability while retaining efficacy. These results reinforce the curative potential of gene editing for HSV disease.

Abstract Background Dental cone beam computed tomography (CBCT) is commonly used to evaluate cancellous bone density before dental implant surgery. However, to our knowledge, no measurement approach has been standardized yet. This study aimed to evaluate the relationship between three different regions of interest (ROI) methods on cancellous bone density at the dental implant site using dental CBCT images. Methods Patients’ dental CBCT images (n = 300) obtained before dental implant surgery were processed using Mimics (Materialise, Leuven, Belgium). At the potential implant sites, the rectangle, cylinder, and surrounding cylinder ROI methods were used to measure bone density. Repeated measures one-way analysis of variance was performed to compare the three ROI methods in terms of measurement results. Pearson correlation analysis was performed to identify the likely pair-wise correlations between the three ROI methods. Results The density value obtained using the surrounding cylinder approach (grayscale value [GV],523.56 ± 228.03) was significantly higher than the values obtained using the rectangle (GV, 497.04 ± 236.69) and cylinder (GV,493 ± 231.19) ROI methods in terms of results. Furthermore, significant correlations were noted between the ROI methods (r > 0.965; p

Abstract Aims This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. Methods Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. Results Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. Conclusion Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

To study temperature and rate-dependent behaviors of molybdenum-rhenium (Mo–Re) alloys, compressive tests at variable temperatures and strain rates were conducted. After the same machining and thermal annealing processes, fully recrystallization happens in Mo and Mo–Re alloys with low Re content (5 wt %), while recovery occurs in Mo–Re alloys with high Re content (14 wt% and 42 wt %). The strength increases as Re content rises at all temperatures (300 °C, 600 °C and 1200 °C), meaning sufficient strengthening effect of Re. The rate-dependent behaviors, however, show different trends between Mo and Mo–Re alloys. Positive strain rate sensitivity is detected in Mo and low Re Mo–Re alloys in all temperatures, which is consistent to other research. While, near zero strain rate sensitivity is found in high Re Mo–Re alloys at 600 °C. Such an unusual phenomenon may be contributed to high stored dislocation density during mechanical processes. The stored dislocations are activated at a proper temperature to accommodate plastic flow, which weakens the influence of strain rate on strength.

Geological hazard forecasting and early warning are crucial measures for preventing geological disasters and minimizing casualties. Since the initiation of geological hazard meteorological risk early warning in 2003, 80% of mountainous provinces, cities and counties in China have implemented such measures. However, the independent construction model at the provincial, city, and county levels is inadequate to meet the collaborative needs across ministries, provinces, and the integration of cities and counties. This paper presents the case of integrated construction of meteorological risk early warning for geological hazards in Zhejiang Province. Following the principle of “provincial forecast extends to county, municipal forecast to township, and county early warning to village (point)”, the integration and exploration of trend forecasting, daily forecasting, short-term forecasting, real-time early warning, and the ‘intelligent prevention of geological disaster’ app have been conducted. A full lifecycle control and prevention business system of geological disaster with visual supervision and closed-loop means of intelligent prevention of geological disaster APP application has been established. Additionally, a digital product system for geological hazard prediction and early warning, tailored to the characteristics of Zhejiang Province, has been developed.

Abstract Background Aconitum carmichaelii Debx. has been widely used as a traditional medicinal herb for a long history in China. It is highly susceptible to various dangerous diseases during the cultivation process. Downy mildew is the most serious leaf disease of A. carmichaelii, affecting plant growth and ultimately leading to a reduction in yield. To better understand the response mechanism of A. carmichaelii leaves subjected to downy mildew, the contents of endogenous plant hormones as well as transcriptome sequencing were analyzed at five different infected stages. Results The content of 3-indoleacetic acid, abscisic acid, salicylic acid and jasmonic acid has changed significantly in A. carmichaelii leaves with the development of downy mildew, and related synthetic genes such as 9-cis-epoxycarotenoid dioxygenase and phenylalanine ammonia lyase were also significant for disease responses. The transcriptomic data indicated that the differentially expressed genes were primarily associated with plant hormone signal transduction, plant-pathogen interaction, the mitogen-activated protein kinase signaling pathway in plants, and phenylpropanoid biosynthesis. Many of these genes also showed potential functions for resisting downy mildew. Through weighted gene co-expression network analysis, the hub genes and genes that have high connectivity to them were identified, which could participate in plant immune responses. Conclusions In this study, we elucidated the response and potential genes of A. carmichaelii to downy mildew, and observed the changes of endogenous hormones content at different infection stages, so as to contribute to the further screening and identification of genes involved in the defense of downy mildew.

Abstract Cancer-directed surgeries (CDS) play a crucial role in prostate cancer (PCa) management along with possible survival and therapeutic benefits. However, barriers such as socioeconomic factors may affect patients’ decision of refusing recommended CDS. This study aimed to uncover risk factors and the impact on survival associated with CDS refusal. We retrospectively reviewed the Surveillance, Epidemiology, and End Results database for patients diagnosed with PCa between 2000 and 2019. Multiple sociodemographic and clinical characteristics were extracted to assess predictors for physicians’ surgical recommendations and patients’ surgical refusal, respectively. Propensity score matching was performed to balance the covariates. The impact of surgical refusal on mortality risk was also investigated. A total of 185,540 patients were included. The physician’s recommendation of CDS was significantly influenced by the patient’s age, race, income, home location, diagnosis year, Gleason score, prostate-specific antigen (PSA), and TNM stage. About 5.6% PCa patients refused CDS, most of whom were older, non-White race, lack of partners, living outside of metropolitan areas, with higher PSA or lower clinical TNM stage. Patients who refused CDS had an increased risk of cancer-specific mortality and overall mortality than those who performed CDS. Physicians may weigh a host of sociodemographic and clinical factors prior to making a CDS recommendation. Patients’ refusal of recommended CDS affected survival and was potentially modifiable by certain sociodemographic factors. Physicians should fully consider the hindrances behind patients’ CDS refusal to improve patient-doctor shared decision-making, guide patients toward the best alternative and achieve better outcomes.

Abstract Background On December 7, 2022, the Joint Prevention and Control Mechanism of China’s State Council released the “Ten New Guidelines” to optimize the coronavirus disease 2019 (COVID-19) prevention policies further. This signaled a broader shift from “dynamic clearing” to “coexisting with the virus” nationwide. Objective This study aims to examine the experiences and perspectives of interdisciplinary nurses during the COVID-19 outbreak in China after the implementation of the “Ten New Guidelines”. The goal is to understand the challenges faced by this unique nursing group and inform organizational support to bolster their well-being and resilience. Methods Two tertiary hospitals in southeastern Zhejiang Province were selected, with interdisciplinary nurses chosen as subjects. A constructivist qualitative research approach was employed, using semi-structured face-to-face interviews. Research data were collected through interviews and analyzed using content analysis. Results Fifteen interdisciplinary nurses were included in this study. The analysis revealed four main themes and nine sub-themes. The main themes were: (1) ineffective organizational support (inadequate organizational care, poor PPE, excessive workload), (2) physiological distress after contracting COVID-19 (extreme physical fatigue, leakage of urine due to severe coughing), (3) fear of being wrong (fear of being reprimanded in public, psychological anxiety), and (4) family responsibility anxiety (difficulty of loyalty and filial piety, obligations to their children). Conclusion We provide new evidence that organizations must proactively address the support, training, and communication needs of staff, particularly interdisciplinary nurses, to supplement epidemic containment. This is also essential in helping mitigate the work-family conflicts such roles can create.

Abstract Temporary neurological dysfunction (TND), a common complication following surgical repair of Type A Aortic Dissection (TAAD), is closely associated with increased mortality and long-term cognitive impairment. Currently, effective treatment options for TND remain elusive. Therefore, we sought to investigate the potential of postoperative relative band power (RBP) in predicting the occurrence of postoperative TND, with the aim of identifying high-risk patients prior to the onset of TND. We conducted a prospective observational study between February and December 2022, involving 165 patients who underwent surgical repair for TAAD at our institution. Bedside Quantitative electroencephalography (QEEG) was utilized to monitor the post-operative brain electrical activity of each participant, recording changes in RBP (RBP Delta, RBP Theta, RBP Beta and RBP Alpha), and analyzing their correlation with TND. Univariate and multivariate analyses were employed to identify independent risk factors for TND. Subsequently, line graphs were generated to estimate the incidence of TND. The primary outcome of interest was the development of TND, while secondary outcomes included intensive care unit (ICU) admission and length of hospital stay. A total of 165 patients were included in the study, among whom 68 (41.2%) experienced TND. To further investigate the independent risk factors for postoperative TND, we conducted both univariate and multivariate logistic regression analyses on all variables. In the univariate regression analysis, we identified age (Odds Ratio [OR], 1.025; 95% CI, 1.002–1.049), age ≥ 60 years (OR, 2.588; 95% CI, 1.250–5.475), hemopericardium (OR, 2.767; 95% CI, 1.150–7.009), cardiopulmonary bypass (CPB) (OR, 1.007; 95% CI, 1.001–1.014), RBP Delta (OR, 1.047; 95% CI, 1.020–1.077), RBP Alpha (OR, 0.853; 95% CI, 0.794–0.907), and Beta (OR, 0.755; 95% CI, 0.649–0.855) as independent risk factors for postoperative TND. Further multivariate regression analyses, we discovered that CPB time ≥ 180 min (OR, 1.021; 95% CI, 1.011–1.032), RBP Delta (OR, 1.168; 95% CI, 1.105–1.245), and RBP Theta (OR, 1.227; 95% CI, 1.135–1.342) emerged as independent risk factors. TND patients had significantly longer ICU stays (p

Abstract Background This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD). Methods A whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software. Results A total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences. Conclusions The present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD.