Search

Localized corrosion poses significant threat to structural integrity. Understanding the kinetics of localized corrosion-induced material morphology changes is crucial to realizing effective corrosion prevention and control and safe structural design. However, the mainstream research tools in this area suffer from various limitations, including inability to examine substrates that are covered by corrosion products (e.g., in situ confocal laser scanning microscopy and in situ optical microscopy) and susceptibility to non-Faradaic current-induced accuracy loss (e.g., wire beam electrode and scanning vibrating electrode technique). In this paper, we introduce an ultrasonic technique that can carry out real-time 3D imaging of localized corrosion-induced material morphology changes in a direct, non-intrusive, and corrosion product-immune manner, circumventing the limitations of the existing research tools. The dedicated experimental specimens for the technique are prepared by permanently installing, on a substrate, a large-scale piezoelectric transducer patch. During an experiment, different zones of the transducer patch are activated in a round-robin fashion to generate ultrasonic waves and acquire reflections. The instantaneous morphologies of the substrate are then reconstructed by processing, via tomography, the reflection signals acquired. A series of localized corrosion experiments were conducted to assess the performance of the technique. The results ascertained the accuracy of the technique, and revealed that the axial resolution of the technique can reach as high as 0.005% of the thickness of the substrate used, and that the lateral resolution of the technique can be enhanced by as simple as exciting ultrasonic waves more closely to each other.

Abstract Objective To assess the prevalence, timing, and functional impact of neuropsychiatric symptoms in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to assess whether these neuropsychiatric symptoms are associated with magnetic resonance imaging (MRI) features of the patients. Methods Our study included a total of 78 patients with CADASIL. To assess neuropsychiatric symptoms, we evaluated the caregivers using the Neuropsychiatric Inventory (NPI). Patients were considered to have an irritability, depression, apathy, aggression, or anxiety disorder if they scored ≥1 in the NPI. Subsequently, we conducted a more detailed assessment of irritability, depression, apathy, aggression, and anxiety. Multivariate logistic regression was employed to analyze the relationships between neuropsychiatric symptoms and clinical/MRI features in the patients. Results Overall, 57.69% of patients with CADASIL experienced neuropsychiatric symptoms. Among these symptoms, irritability was the most prevalent (52.56%), followed by depression (19.23%), apathy (17.95%), aggression (7.69%), and anxiety (6.41%). The mean age of onset for irritability was the youngest, followed by anxiety, apathy, aggression, and depression. Among patients with both stroke/TIA and neuropsychiatric symptoms, 31.03% reported experiencing neuropsychiatric symptoms prior to stroke/TIA. Furthermore, both irritability and apathy had a negative impact on the patients' daily functioning. Additionally, there was a correlation between the presence of neuropsychiatric symptoms and the patients' MRI lesion burden. Interpretation Our study has discovered that neuropsychiatric symptoms are highly prevalent in patients with CADASIL and may occur before cerebrovascular events, suggesting that neuropsychiatric symptoms of CADASIL deserve more attention and earlier exploration.

Abstract Background The incidence of androgenetic alopecia in males is on the rise annually, with hair transplantation using follicular unit extraction (FUE) gaining increasing acceptance as an appropriate treatment for these individuals. Methods A retrospective study was undertaken, involving 158 male patients diagnosed with androgenetic alopecia, who underwent treatment between January 2016 and December 2020 at the Medical Cosmetology Department of the First Affiliated Hospital of Xi’an Medical University. Demographic data and treatment characteristics were documented and analyzed. Clinical efficacy, operation-related complications, patient satisfaction rates, and quality of life scores were assessed and analyzed. Results Following FUE hair transplantation, over 90% of the hair follicles survived in 158 patients, with more than 85% of patients achieving a hair follicle survival rate exceeding 95% at 12 months post-operation. Patient satisfaction rates exceeded 98%, while the complication rate was below 6%. Conclusion Our findings demonstrate that FUE is a minimally invasive hair transplant technique associated with a high hair follicle survival rate and optimal hair density. This approach proves effective in treating male androgenetic alopecia and merits further clinical application.

Abstract Mitochondria, as the cellular end-users of oxygen and responsible for approximately 98% of total body oxygen consumption, play a significant role in the development of organ dysfunction during shock. Therefore, integrating information on mitochondrial oxygen homeostasis with macroscopic observations of macrocirculation and microcirculation is crucial for monitoring critically ill patients or those undergoing high-risk surgery. However, current clinical practice still lack reliable surrogate parameters for assessing mitochondrial function. The Cellular Oxygen METabolism (COMET) monitor, utilizing the protoporphyrin IX triplet state lifetime technique (PpIX-TSLT), represents the first clinical device capable of non-invasive, in vivo measurement of mitochondrial oxygen pressure and oxidative phosphorylation. Recent research suggests that implementing this real-time bedside monitoring will provide additional insights into microcirculatory dynamics and enhance patient management. This review will comprehensively detail the rationale, methodologies, evolution, and clinical applications of the technique, aiming at improving the understanding of mitochondrial pathology in daily clinical practice and facilitating the development of targeted therapeutic strategies. Graphical Abstract

Abstract A TOPAS-based optimization program has been developed to precisely concentrate the dose of focused very-high-energy electron (VHEE) beams on deep-seated targets. This is accomplished by optimizing the magnetic gradients, positions, and number of quadrupole magnets within TOPAS. Using only three quadrupole magnets, the program focuses 250 MeV VHEE beams to achieve a maximum dose position deeper than 17 cm, while maintaining entrance and exit doses within 25% and limiting the lateral dimensions to ≤ 1 cm at the maximum dose location. The linear relationship between the magnetic gradient of the last quadrupole magnet and the maximum dose position enables dose location adjustments through gradient variation. Multiple positions were validated in TOPAS with errors within 1%. The spread-out electron peak (SOEP) is achieved by combining two VHEE beams with different maximum dose positions using the differential evolution method, covering a target depth of 12–17 cm and attaining a dose flatness better than 99%. This pioneering program imposes constraints on entrance dose, exit dose, maximum dose position, and the lateral dimensions of dose deposition at the maximum dose position within phantom. This program may be a promising tool in the applications of focused VHEE in highly conformal treatment plans based on TOPAS.

Abstract To determine diagnostic value of diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS) patients and investigate the association between DTI and neurofilaments (NFs), including serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH). Forty-three clinically diagnosed ALS patients and 32 control subjects without neurological disorders underwent routine MRI (magnetic resonance imaging) and DTI scans. DTI parameters (mean diffusivity [MD] and fractional anisotropy [FA]) at axial levels of internal capsules and cerebral peduncles along the corticospinal tract (CST) were measured. The study compared the differences of DTI parameters between ALS patients and controls using the Mann-Whitney U test. Diagnostic efficacy of each DTI metric was evaluated using the receiver operating characteristic (ROC) curve. NFs (NFL and pNFH levels in serum and CSF) were measured by enzyme-linked immunosorbent assay. Correlation analyses were conducted between DTI parameters and NFs. Capsule-MD and Peduncle-MD in ALS patients were higher than those in controls; whereas Capsule-FA and Peduncle-FA in ALS patients were lower than those in controls (all, p

Abstract A dual-band broadband absorber based on frequency selective surface (FSS) is proposed. This double-layer absorber consists of two layers of FSS structure; each layer has a unique construction and plays its wave-absorbing function in different frequency bands. In the low-frequency band, layer I is a transmission channel, and layer II effectively absorbs electromagnetic waves. Furthermore, layer I exhibits significant absorption characteristics in the high-frequency band, whereas layer II provides effective reflection. The combination of the two layers results in a remarkably effective absorption. Its reflectivity below − 10 dB covers a bandwidth of 5.5–14.8 GHz and 22.9–33.1 GHz, and its fractional bandwidth is 128%. The structure prevents external electromagnetic interference from affecting the antenna’s performance, ensuring communication quality in critical frequency bands while reducing unwanted absorption in unwanted frequency bands. It is worth mentioning that the structure still has good stability under 45° oblique incidence. The physical mechanism is analyzed in detail by using an equivalent circuit model (ECM). The measurement results are in good agreement with those of simulation and ECM.

Abstract Embedded Dynamic RAM (eDRAM) has become a key solution for large-capacity cache in high-performance processors. A heterogeneous two transistor capacitorless eDRAM (2T-eDRAM) that combines silicon and molybdenum disulfide (MoS2) is reported to address the short retention issue in conventional gain cell (GC) eDRAMs meanwhile eliminate the pillar capacitor in one transistor and one capacitor (1T1C) eDRAMs. The MoS2 write transistor with low OFF current (IOFF) enables long data retention, while the Si read transistor offers high drive current and logic compatibility. This combination enhances data retention by 1000 times and sense margin by 100 times respectively compared to full Si and MoS2 counterparts. A three-dimensional (3D) design stacking MoS2 on Si is demonstrated with back-end-of-line (BEOL) process to double integration density. With 6000 s data retention, 35 μA/μm sense margin, 5 ns access speeds, 3D integration and CMOS logic compatibility, this Si-MoS2 eDRAM marks a significant advancement in memory technology.

Abstract Protein-rich diets shorten lifespan but increase fecundity in many organisms. Animals actively adjust their feeding behavior to meet their nutritional requirements. However, the neural mechanisms underlying the dynamic regulation of protein consumption remain unclear. Here we find that both sexes of fruit flies exhibit a preference for protein food before mating to prepare for reproduction. Mated female flies display an increased appetite for yeast to benefit their offspring, albeit at the cost of stress resistance and lifespan. In contrast, males show a momentarily reduced yeast appetite after mating likely to restore their fitness. This mating state-dependent switch between sexes is mediated by a sexually dimorphic neural circuit labeled with leucokinin in the anterior brain. Furthermore, intermittent yeast consumption benefits both the lifespan and fecundity of males, while maximizing female fecundity without compromising lifespan.

Abstract Atmospheric rivers (ARs) are characterized by intense lower tropospheric plumes of moisture transport that are frequently responsible for midlatitude wind and precipitation extremes. The prediction of ARs at subseasonal-to-seasonal (S2S) timescales is currently at a low level of skill, reflecting a need to improve our understanding of their underlying sources of predictability. Based on 20 year hindcast experiments from the Geophysical Fluid Dynamics Laboratory’s SPEAR S2S forecast system, we evaluate the S2S prediction skill of AR activities in the northern winter. Higher forecast skill is detected for high-frequency AR activities (3–7 days/week) compared to low-frequency AR activities (1–2 days/week), even though the occurrence rate of high-frequency ARs exceeds that of low-frequency ARs. For the first time, we have applied the Average Predictability Time technique to the SPEAR system to identify the three most predictable modes of AR in the North Pacific sector. These modes can be attributed to the influences of the El Niño–Southern Oscillation, the Pacific North American pattern, and the Arctic Oscillation. S2S AR forecast skill in western United States is modulated by various phases of large-scale variability. This study highlights potential windows of opportunity for operational S2S AR forecasting.

Abstract Background Modulating the microbiome with nanomaterials has been proposed to improve plant growth, and reduce reliance on external inputs. Carbon Nanosol (CNS) was attracted for its potential to improve plant productivity. However, the mechanism between CNS and rhizosphere microorganisms remained largely elusive. Results Here, we tried to systematically explore the effects of CNS (600 and 1200 mg/L by concentration) on tobacco growth, soil physical properties, and root-associated microbiome. The influence of CNS on soil physicochemical properties and plant growth was significant and dose-dependent, leading to a 28.82% increase in biomass accumulation by 600 mg/L CNS. Comparison between the CNS-treated and control plants revealed significant differences in microbiome composition, including 1148 distinct ASVs (923 bacteria and 225 fungi), microbiome interactions, and metabolic function of root-associated microbiomes. Fungal and bacterial communities had different response patterns for CNS treatment, with phased and dose-dependent effects, with the most significant changes in microbial community structure observed at 1200 mg/L after 10 days of treatment. Microbial networks of CNS-treated plants had more nodes and edges, higher connectivity, and more hub microorganisms than those of control plants. Compared with control, CNS significantly elevated abundances of various bacterial biomarkers (such as Sphingomonas and Burkholderia) and fungi biomarkers (including Penicillium, Myceliophthora, and Talaromyces), which were potential plant-beneficial organisms. Functional prediction based on metagenomic data demonstrated pathways related to nutrient cycling being greatly enriched under CNS treatment. Furthermore, 391 culturable bacteria and 44 culturable fungi were isolated from soil and root samples. Among them, six bacteria and two fungi strains enriched upon CNS treatment were validated to have plant growth promotion effect, and two fungi (Cladosporium spp. and Talaromyces spp.) played their roles by mediating volatile organic compounds (VOCs). To some extent, the driving and shaping of the microbiome by CNS contributed to its impact on plant growth and development. Conclusion Our results revealed the key role of root-associated microbiota in mediating the interaction between CNS and plants, thus providing valuable insights and strategies for harnessing CNS to enhance plant growth. Graphical Abstract

Abstract The active power control of photovoltaic (PV) inverters without energy storage can flatten the fluctuating power and support the voltage amplitude and frequency of the grid. When operated in grid‐forming voltage‐control mode, because the PV power can change rapidly and widely, the PV inverter needs to track the power commands quickly and precisely. Traditionally, this goal is achieved with the estimation of PV power curve or PI‐based multiple‐loop feedback control, where flexibility, availability and accuracy are not satisfactory. Therefore, a CC/VC‐based power tracking (CVPT) method is proposed, which only uses single‐loop in control. The proposed method does not need to tune multiple loops and can respond faster, which is important for grid‐forming voltage control. Furthermore, the different operating modes due to the limitation of PV maximum power are analysed, and a mode switch method is proposed. Simulation and experimental results demonstrate that the PV inverter can cope with power disturbances from both the power and grid sides and maintain the quality of grid voltage.

Abstract Malignant bone tumors, which are difficult to treat with current clinical strategies, originate from bone tissues and can be classified into primary and secondary types. Due to the specificity of the bone microenvironment, the results of traditional means of treating bone tumors are often unsatisfactory, so there is an urgent need to develop new treatments for malignant bone tumors. Recently, nanoparticle-based approaches have shown great potential in diagnosis and treatment. Nanoparticles (NPs) have gained significant attention due to their versatility, making them highly suitable for applications in bone tissue engineering, advanced imaging techniques, and targeted drug delivery. For diagnosis, NPs enhance imaging contrast and sensitivity by integrating targeting ligands, which significantly improve the specific recognition and localization of tumor cells for early detection. For treatment, NPs enable targeted drug delivery, increasing drug accumulation at tumor sites while reducing systemic toxicity. In conclusion, understanding bone microenvironment and using the unique properties of NPs holds great promise in improving disease management, enhancing treatment outcomes, and ultimately improving the quality of life for patients with malignant bone tumors. Further research and development will undoubtedly contribute to the advancement of personalized medicine in the field of bone oncology.

In order to explore the law of selective laser melting (SLM) forming of Nitinol alloy, and obtain high quality additive manufacturing parameters of Nitinol alloy, a series of single-track SLM experiments on Nitinol alloy were conducted under different combined parameters of laser power and scanning speed. The effects of laser power, scanning speed and linear energy density on track forming, molten pool evolution and pore formation were systematically discussed by characterizing the track trajectory, molten pool morphology, dimensions and defects of the molten pool, and the ideal process parameters were obtained. The experimental results revealed that the average track width and width uniformity decreased with the increase of the scanning speed, the spheroidization phenomenon and height fluctuation became more pronounced, and the phenomena of necking, subsection and interruption increased significantly at the fixed laser power. Under the fixed scanning speed, the width, height and width uniformity of the molten track gradually increased with the increase of the laser power, and the phenomena of spheroidization, subsection and interruption gradually reduced. Moreover, the upper zone of the molten pool is shaped like an inverted bowl, and the lower zone is mainly divided into five categories, which are lack of fusion, shallow bowl shape, deep bowl shape, keyhole shape and deeper keyhole shape under different process parameters. The defects of the molten pool mainly include lack of fusion and trapped gas. An ideal molten pool without defects can be obtained under the parameter conditions of 100–150W laser power and 100–200 mm/s spanning speed.

Infected wounds pose a significant clinical challenge due to bacterial resistance, recurrent infections, and impaired healing. Reactive oxygen species (ROS)-based strategies have shown promise in eradicating bacterial infections. However, the excess ROS in the infection site after treatments may cause irreversible damage to healthy tissues. To address this issue, we developed bovine serum albumin-iridium oxide nanoclusters (BSA-IrOx NCs) which enable photo-regulated ROS generation and scavenging using near infrared (NIR) laser. Upon NIR laser irradiation, BSA-IrOx NCs exhibit enhanced photodynamic therapy, destroying biofilms and killing bacteria. When the NIR laser is off, the nanoclusters' antioxidant enzyme-like activities prevent inflammation and repair damaged tissue through ROS clearance. Transcriptomic and metabolomic analyses revealed that BSA-IrOx NCs inhibit bacterial nitric oxide synthase, blocking bacterial growth and biofilm formation. Furthermore, the nanoclusters repair impaired skin by strengthening cell junctions and reducing mitochondrial damage in a fibroblast model. In vivo studies using rat infected wound models confirmed the efficacy of BSA-IrOx NCs. This study presents a promising strategy for treating biofilm-induced infected wounds by regulating the ROS microenvironment, addressing the challenges associated with current ROS-based antibacterial approaches.

Abstract Alternative cleavage and polyadenylation within introns (intronic APA) generate shorter mRNA isoforms; however, their physiological significance remains elusive. In this study, we developed a comprehensive workflow to analyze intronic APA profiles using the mammalian target of rapamycin (mTOR)-regulated transcriptome as a model system. Our investigation revealed two contrasting effects within the transcriptome in response to fluctuations in cellular mTOR activity: an increase in intronic APA for a subset of genes and a decrease for another subset of genes. The application of this workflow to RNA-seq data from The Cancer Genome Atlas demonstrated that this dichotomous intronic APA pattern is a consistent feature in transcriptomes across both normal tissues and various cancer types. Notably, our analyses of protein length changes resulting from intronic APA events revealed two distinct phenomena in proteome programming: a loss of functional domains due to significant changes in protein length or minimal alterations in C-terminal protein sequences within unstructured regions. Focusing on conserved intronic APA events across 10 different cancer types highlighted the prevalence of the latter cases in cancer transcriptomes, whereas the former cases were relatively enriched in normal tissue transcriptomes. These observations suggest potential, yet distinct, roles for intronic APA events during pathogenic processes and emphasize the abundance of protein isoforms with similar lengths in the cancer proteome. Furthermore, our investigation into the isoform-specific functions of JMJD6 intronic APA events supported the hypothesis that alterations in unstructured C-terminal protein regions lead to functional differences. Collectively, our findings underscore intronic APA events as a discrete molecular signature present in both normal tissues and cancer transcriptomes, highlighting the contribution of APA to the multifaceted functionality of the cancer proteome.

Efficient Convolution Operator (ECO) algorithms have achieved impressive performances in visual tracking. However, its feature extraction network of ECO is unconducive for capturing the correlation features of occluded and blurred targets between long-range complex scene frames. More so, its fixed weight fusion strategy does not use the complementary properties of deep and shallow features. In this paper, we propose a new target tracking method, namely ECO++, using deep feature adaptive fusion in a complex scene, in the following two aspects: First, we constructed a new temporal convolution mode and used it to replace the underlying convolution layer in Conformer network to obtain an improved Conformer network. Second, we adaptively fuse the deep features, which output through the improved Conformer network, by combining the Peak to Sidelobe Ratio (PSR), frame smoothness scores and adaptive adjustment weight. Extensive experiments on the OTB-2013, OTB-2015, UAV123, and VOT2019 benchmarks demonstrate that the proposed approach outperforms the state-of-the-art algorithms in tracking accuracy and robustness in complex scenes with occluded, blurred, and fast-moving targets.

Abstract The classification and recognition of underwater targets by an active sonar system remain challenging and complex. Traditional methods have limited classification performance in time and spatially varying ocean channels. An active sonar target recognition method is proposed based on multi‐domain transformations and an attention‐based fusion network. Initially, the active target echo undergoes time‐frequency analysis, auditory signal processing, and matched filtering to represent target attributes in joint spatial‐time‐frequency domains. Subsequently, multiple attention‐based fusion models fuse the multi‐domain transformations either early or late in the processing stages. An attention module further enhances significant feature channels through adaptive weight assignment. Experiment results demonstrate that the recognition accuracy of active sonar echoes using multi‐domain transformations improves significantly compared to that of single‐domain methods, with an increase of up to 10.5%. The incorporation of multiple transformation domains provides complementary information about the target, thereby enhancing the network's representation ability, especially with limited data samples. Furthermore, the findings indicate that feature fusion of multiple transformations in a high‐level feature space yields more informative and effective results for active sonar echoes compared to low‐level feature spaces.

Abstract Background Keloids are currently challenging to treat because they recur after resection which may affect patients’ quality of life. At present, no universal consensus on treatment regimen has been established. Thus, finding new molecular mechanisms underlying keloid formation is imminent. This study aimed to explore the function of secreted protein acidic and cysteine rich (SPARC) on keloids and its behind exact mechanisms. Methods The expression of SPARC, p38γ, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), α-SMA, and Ki67 in patients with keloid and bleomycin (BLM)-induced fibrosis mice was assessed utilizing western blot, qRT-PCR, and immunohistochemical staining. After transfected with pcDNA-SPARC, si-SPARC-1#, si-SPARC-2#, and si-p38γ, and treated with glycolytic inhibitor (2-DG) or p38 inhibitor (SB203580), CCK-8, EdU, transwell, and western blot were utilized for assessing the proliferation, migration, and collagen production of keloid fibroblasts (KFs). Results SPARC, p38γ, and PFKFB3 were highly expressed in patients with keloid and BLM-induced fibrosis mice. SPARC promoted the proliferation, migration, and collagen production of KFs via inducing glycolysis. Moreover, SPARC could activate p38γ signaling to stabilize PFKFB3 protein expression in KFs. Next, we demonstrated that SPARC promoted the proliferation, migration, collagen production, and glycolysis of KFs via regulating p38γ signaling. In addition, in BLM-induced fibrosis mice, inhibition of p38γ and PFKFB3 relieved skin fibrosis. Conclusions Our findings indicated that SPARC could activate p38γ pathway to stabilize the expression of PFKFB3, and thus promote the glycolysis of KFs and the progression of keloid.

Abstract Ultra-high performance concrete (UHPC) is becoming a prevailing construction material in protective engineering. However, an insufficient research basis causes difficulty in the anti-explosion structural design of UHPC. To investigate the blast resistance of the UHPC slab (UHPCS), contact explosion tests were carried out. UHPCS exhibited superior blast resistance and a lower threshold range of failure modes than the normal reinforced concrete slab (NRCS). Compared with the NRCS, the UHPCS reached a lower damage level under the same scaled distance and had smaller craters and spalls, fewer cracks, and an absence of cross-shaped cracks. For NRCS, failure modes of medium spall, severe spall, and perforation were reached under charges of 1.0, 1.6, and 2.2 kg. In contrast, UHPCS reached medium spall, severe spall, and perforation under charges of 1.6, 3.3, and 5.0 kg. The scaled slab thicknesses (T/W1/3) of the medium spall, severe spall, and perforation of the NRCSs were 1.17, 1.27, and 1.32 times larger than those of the UHPCSs, respectively. The formulae for predicting the spall and perforation thresholds of the UHPCSs were proposed. The reduction factors were used to evaluate the mitigation effect of the blast damage on the UHPC compared to that on the NRC. The reduction factors of the crater diameter ( $${\gamma _\Phi }_{C}$$ ) and the spall diameter ( $${\gamma _{\Phi s}}$$ ) were determined to be 0.507 and 0.721, respectively. For quantitative analysis of the anti-explosion performance of UHPC, a simple estimation method for predicting the dimensions of the crater and spall of the UHPCS was proposed and verified based on the dimensional analysis method.

Abstract The construction of soft robots’s models and controllers remains a significant challenge. In this paper, we propose a new walking control method for the quadruped soft robot named genetic algorithm-optimized PID. First, we construct the control model correlating valve voltage with leg bending based on the geometrical analysis. This modeling approach leverages the characteristics of novel leg structure and bend sensor, thereby streamlining the control model for locomotion of quadruped soft robotic. Moreover, We apply the genetic algorithm to automatically tune parameters and optimize PID controllers, aiming to enhance control performance. The application of the proposed method to the walking control has been uniquely demonstrated on a real 3D-printed quadruped soft robot. Experimental results indicate that the genetic algorithm-optimized PID controller significantly improves trajectory tracking compared to the Ziegler-Nichols tuning method. This optimization increases the robot’s walking speed from 5 mm/s to 8 mm/s, reduces the error rate by 2.4064%, decreases overshoot by 12.55%, and shortens response time by 0.5 s, substantially enhancing the controller’s overall performance. Additionally, compared to particle swarm optimization, the proposed method further improves performance by reducing the error rate by 0.4079%, overshoot by 8.4%, and response time by 1.0 s.

Abstract Background To evaluate the efficacy and safety of anlotinib combined with chemotherapy in the treatment of advanced soft tissue sarcoma (STS). Methods A total of 14 patients with advanced STS consisting of 4 liposarcoma, 3 undifferentiated polymorphous sarcoma, 2 synovial sarcoma, 1 Extraosseous ewing sarcoma, 1 spindle cell sarcoma, 1 Sarcomatoid malignant mesothelioma, 1 hemangiosarcoma, and 1 fibrosarcoma, were treated with anlotinib plus chemotherapy. The anlotinib was combined with chemotherapy as the first-line treatment in 13 patients, and as second-line treatment in 1 patient. Chemotherapy regimens were based on anthracyclines and ifosfamide, and other drugs included paclitaxel, and so on. Efficacy and safety were evaluated every 2 treatment cycles. Results According to the stage of AJCC, 9 patients were stage III and 5 patients were stage IV. The average cycle of treatment is 3.86. Among the 14 patients, 2 cases had received surgical treatment after neoadjuvant chemothrapy, 5 cases had partial response (PR), 7 cases had stable disease (SD), and 2 cases had progressive disease (PD). The overall response rate (ORR) was 35.7% (5/14). Patients who had not underwent surgical treatment were with a disease control rate (DCR) of 83.3% (10/12). The median progression free survival (PFS) was 8.25 months. The common treatment-related adverse effects included bone marrow suppression, nausea, vomiting and hypertension. Three patients had severe adverse effect, which was febrile neutropenia. No treatment-related death was found. Conclusions Anlotinib combined with chemotherapy in the treatment of STS is effective and tolerable, which is a promising strategy. It is worthy of further clinical research.

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

Abstract Metabolic reprogramming is a pivotal biological process in which cellular metabolic patterns change to meet the energy demands of increased cell growth and proliferation. In this review, we explore metabolic reprogramming and its impact on fibrotic diseases, providing a detailed overview of the key processes involved in the metabolic reprogramming of renal fibrosis, including fatty acid decomposition and synthesis, glycolysis, and amino acid catabolism. In addition, we report that Chinese medicine ameliorates renal inflammation, oxidative stress, and apoptosis in chronic kidney disease by regulating metabolic processes, thereby inhibiting renal fibrosis. Furthermore, we reveal that multiple targets and signaling pathways contribute to the metabolic regulatory effects of Chinese medicine. In summary, this review aims to elucidate the mechanisms by which Chinese medicine inhibits renal fibrosis through the remodeling of renal cell metabolic processes, with the goal of discovering new therapeutic drugs for treating renal fibrosis.

Objectives: The guidelines recommend fractional flow reserve-guided coronary artery bypass grafting (CABG) during primary valve surgery without evidence. Quantitative flow ratio (QFR) is a novel coronary angiography (CAG)-based fractional flow reserve measurement. We aimed to compare the early clinical outcomes between QFR-guided and CAG-guided CABG in these patients. Methods: This observational study screened all 2081 patients admitted to our institution for elective primary mitral and/or aortic valve surgery from January 2017 to September 2020. Of them, all 188 patients with comorbid coronary artery lesions (visual estimated stenosis ≥50%) were included. Sixty-nine patients with QFR analysis received bypasses only for lesions with QFR ≤0.80 (QFR-guided group). The remaining 119 patients without QFR analysis received bypasses for all stenosis ≥50% (CAG-guided group). Propensity overlap weighting was used to neutralize the intergroup imbalance. The primary end point was major adverse cardiovascular events. Results: After propensity score weighting, the baseline characteristics were comparable. Concomitant coronary artery bypass grafting was performed 58.1% versus 100% in the QFR-guided and CAG-guided groups, respectively. The mean number of grafts was significantly lower in QFR-guided group than in the CAG-guided group (0.9 ± 0.7 vs 1.6 ± 0.5 [P

Abstract Background The study aimed to compare the clinical outcomes of robotic right colectomy (RRC) versus laparoscopic right colectomy (LRC) in patients diagnosed with right colon cancer, given the increasing adoption of robotic surgical techniques and their potential benefits in oncologic surgery. Methods This retrospective comparative study included patients who underwent right colectomy at Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, between January 2019 and May 2022. The primary outcomes measured were the number of lymph nodes harvested. Key secondary outcomes included the operation time, intraoperative blood loss, postoperative complications, hospitalization costs, overall survival (OS), and disease-free survival (DFS). Data were analyzed using multivariable Cox proportional hazards regression to adjust for potential confounders. Results A total of 225 patients (aged 65.23 ± 11.45, 108 males) with right colon cancer were included, with 100 (44.4%) patients underwent RRC. Patients who underwent RRC had significantly more lymph nodes harvested (27.69 ± 12.59 vs. 24.43 ± 9.42, P = 0.028), and incurred higher total hospitalization costs compared to those with LRC (9.68 ± 7.12 vs. 5.28 ± 1.23 ten-thousand-yuan, P 0.05) within a median follow-up of 27 (range, 9–44) months. Multivariable cox proportional hazards regression showed that patients underwent RRC had significantly higher risk for all-cause death compared with those underwent LRC [hazards ratio (HR) = 2.303, 95% confidence intervals (CI): 1.625–3.265, P

Abstract Defective renal excretion and increased production of uric acid engender hyperuricemia that predisposes to gout. However, molecular mechanisms underlying defective uric acid excretion remain largely unknown. Here, we report a rare genetic variant of gout-unprecedented NUMB gene within a hereditary human gout family, which was identified by an unbiased genome-wide sequencing approach. This dysfunctional missense variant within the conserved region of the NUMB gene (NUMBR630H) underwent intracellular redistribution and degradation through an autophagy-dependent mechanism. Mechanistically, we identified the uric acid transporter, ATP Binding Cassette Subfamily G Member 2 (ABCG2), as a novel NUMB-binding protein through its intracellular YxNxxF motif. In polarized renal tubular epithelial cells (RTECs), NUMB promoted ABCG2 trafficking towards the apical plasma membrane. Genetic loss-of-function of NUMB resulted in redistribution of ABCG2 in the basolateral domain and ultimately defective excretion of uric acid. To recapitulate the clinical situation in human gout patients, we generated a NUMBR630H knock-in mouse strain, which showed marked increases of serum urate and decreased uric acid excretion. The NUMBR630H knock-in mice exhibited clinically relevant hyperuricemia. In summary, we have uncovered a novel NUMB-mediated mechanism of uric acid excretion and a functional missense variant of NUMB in humans, which causes hyperuricemia and gout.

Abstract Bile acids (BAs) exert a profound influence on the body’s pathophysiology by intricately shaping the composition of gut bacteria. However, the complex interplay between BAs and gut microbiota has impeded a systematic exploration of their impact on intestinal bacteria. Initially, we investigated the effects of 21 BAs on the growth of 65 gut bacterial strains in vitro. Subsequently, we examined the impact of BAs on the overall composition of intestinal bacteria, both in vivo and in vitro. The results unveiled distinct effects of various BAs on different intestinal strains and their diverse impacts on the composition of gut bacteria. Mechanistically, the inhibition of intestinal strains by BAs occurs through the accumulation of these acids within the strains. The intracellular accumulation of deoxycholic acid (DCA) significantly influenced the growth of intestinal bacteria by impacting ribosome transcription and amino-acid metabolism. The metabolomic analysis underscores the pronounced impact of DCA on amino-acid profiles in both in vivo and in vitro settings. This study not only elucidates the effects of BAs on a diverse range of bacterial strains and their role in shaping the gut microbiota but also reveals underlying mechanisms essential for understanding and maintaining a healthy gut microbiota.

Abstract High signal-to-noise ratio (SNR) seismic waveform data are conductive to various studies in seismology. Seismic denoising aims to enhance SNR by eliminating additive noise through signal processing while preserving important features of the seismic signal. Conventional parametric seismic denoising methods often require selecting appropriate parameters to achieve optimal results, which may be limiting when dealing with various types and scales of seismic data. Here, we develop an adaptive parameter-free denoising method by combining general cross-validation (GCV) thresholding and pixel connectivity in synchrosqueezed (SS) domain. In this denoising framework, the synchrosqueezed continuous wavelet transform (SS-CWT) is first applied to obtain a high-resolution time–frequency representation. Then, the GCV approach, which allows for choosing the (nearly) optimal threshold without relying on any prior knowledge about the noise level, is employed to attenuate most of the low-energy noise. After that, the relatively isolated high-energy residual noise remaining in the SS-CWT spectrum is removed using pixel connectivity thresholding. Finally, the inverse SS-CWT is applied to the thresholded spectrum to obtain the denoised seismic record. As the thresholds for GCV and pixel connectivity are derived from the spectrum characteristics of the data being analyzed, the proposed denoising approach is highly adaptive and parameter-free. We demonstrate the effectiveness and versatility of the proposed denoising framework using synthetic data and real seismic data from diverse monitoring scenarios, including land, ocean, and emerging distributed acoustic sensing (DAS). The results indicate that the method is a stable and efficient tool for seismic data denoising. Graphical Abstract

Abstract Purpose Accurate detection and resection of the epileptogenic zone (EZ) in patients with long-term epilepsy-associated tumors (LEATs) are significantly correlated with favorable seizure prognosis. However, the relationship between tumors and the EZ remains unknown. This study aimed to evaluate the spatial relationship between LEATs and the EZ, as well as the electrophysiological features of LEATs. Methods We retrospectively studied five patients with LEATs who underwent deep electrode implantation and EZ resection in the hospital. The clinical characteristics, surgical outcomes, localizing features and intracranial SEEG results were reviewed. Results One female and four males (mean age: 25.2 years; median age: 24 years; range: 13–45 years) were included in the study. Five-to-eleven electrodes (mean: 8.4) were implanted per patient. The EZ was located in the tumor and nearby cortex in three cases and in the tumor and distant areas in two cases. Pathological examination revealed ganglioglioma in four cases, two of which were associated with hippocampal sclerosis, and the other case showed a multinodular and vacuolating neuronal tumor with gliosis. All patients were seizure-free for at least 24 months postoperatively. Conclusions SEEG provides valuable insights into the electrophysiological mechanisms of LEATs. The EZ often contains brain tissue around the tumor. However, only a few cases, particularly those with temporoparietal occipital (TPO) area involvement, a long history of epilepsy and other abnormalities on MRI, such as hippocampal sclerosis and focal cortical dysplasia, may include distant areas.

Abstract Prostate cancer is one of the most common cancers in men and poses a significant threat to global male health. Traditional prostate cancer assessment methods have certain limitations, necessitating the identification of new prognostic factors and treatment targets. Our study revealed that low expression of the cornichon family AMPA receptor auxiliary protein 2 (CNIH2) gene was associated with a better progression-free survival rate in prostate cancer patients. The area under the receiver operating characteristic (ROC) curve (AUC) showed that the prognostic ability of the CNIH2 gene was high at 1, 3, and 5 years. The gene was an independent prognostic factor according to multivariate analysis. Functional verification experiments showed that knocking down the CNIH2 gene could inhibit the proliferation, migration and invasion of prostate cancer cells and could also inhibit tumor growth in nude mice. Our study is the first to reveal the important role of the CNIH2 gene in prostate cancer. This discovery provides a new research direction for individualized treatment and prognostic evaluation of prostate cancer.

Abstract Diagnosing Sjogren’s syndrome requires considerable time and effort from physicians, primarily because it necessitates rigorously establishing the presence lymphatic infiltration in the pathological tissue of the labial gland. The aim of this study is to use deep learning techniques to overcome these limitations and improve diagnostic accuracy and efficiency in pathology. We develop an auxiliary diagnostic system for Sjogren’s syndrome. The system incorporates the state-of-the-art object detection neural network, YOLOv8, and enables the precise identification and flagging of suspicious lesions. We design the multi-dimensional attention module and S-MPDIoU loss function to improve the detection performance of YOLOv8. By extracting features from multiple dimensions of the feature map, the utilization of the multi-dimensional attention mechanism enhances the feature interaction across disparate positions, enabling the network to proficiently learn and retain salient cell features. S-MPDIoU introduces an angle penalty term that efficiently minimizes the diagonal distance between predicted and ground truth boxes. Additionally, it incorporates a flexible scale factor tailored to different size feature maps, which balances the issue of sudden gradient decrease during high overlap, thereby accelerating the overall convergence rate. To verify the effectiveness of our methods, we create a dataset of lymphocytes using labial gland biopsy pathology images collected from YanTaiShan hospital and trained the model with this dataset. The proposed model is assessed using standard metrics like precision, recall, mAP. The improved model achieves an increase in recall by 9.1%, mAP.5 by 3.2%, and mAP.95 by 2%. The study demonstrated deep learning’s potential to analysis pathology images, offering a reference framework for the application of deep learning technology in the medical domain.

Abstract Background Previous studies have suggested a significant association between mobile phone addiction (MPA) and non-suicidal self-injury (NSSI) in general adolescents. However, limited research has analyzed this relationship in clinical populations, such as those with major depressive disorder (MDD), and the potential mediation mechanisms remain unclear. Methods This cross-sectional observational study analyzed data from 2343 adolescents with MDD (77.9% females; mean age = 14.99 years, SD = 1.65). Using mediation models, we explored the roles of self-esteem and depression severity (measured by Patient Health Questionnaire-9) in the relationship between MPA and NSSI. Additionally, we evaluated the associations between existing school-implemented mobile phone usage policies and levels of MPA, self-esteem, depression symptoms, and NSSI. Results MPA was significantly associated with NSSI, with low self-esteem and increased depression severity almost entirely mediating this effect (log-odds = 0.016, 95%CI = 0.02–0.013). Subdomains of MPA, including inability to control craving, feelings of anxiety, and productivity loss, followed similar mediation models, while the subdomain of withdrawal/escape had a partial effect mediated by depression severity. Additionally, enforced restrictions on mobile phone usage in schools did not show positive effects on related variables and even exacerbated MPA by increasing cravings and reducing productivity. Conclusion Our study suggests that MPA in adolescents with MDD may be an important risk factor for NSSI occurrence, and that reducing the negative impact of mobile phone usage on self-esteem and depressive symptoms, rather than simply restricting usage, may be crucial for effective intervention.

Abstract This study aims to identify the conceptualisation of overall well-being used for well-being assessment through a review of the characteristics and key components and/or dimensions of well-being scales as presented in current literature. Scopus and Web of Science were searched, and thematic analysis was conducted inductively to analyse the identified components within scales, as well as the types of well-being these scales measure. 107 peer-reviewed articles from 2003 to 2022 were included, and 69 well-being scales were identified covering nine areas of well-being. Four final themes were identified as the foundational dimensions of overall well-being: hedonic; eudaimonic; physical health; and generic happiness. Notably, these 69 scales are mainly validated and adopted in the Western context. ‘4 + N’ frameworks of overall well-being are recommended for assessing overall well-being. This review provides researchers with a synthesis of what types of well-being have been measured and which measures have been used to assess these types of well-being for which research participants. Non-Western-based well-being research is called for that incorporates a broader range of research participants and cultural contexts in contributing to a more inclusive understanding of well-being.

Abstract We investigated a diffraction optical waveguide structure with a double layer coupling configuration. This double layer-coupled diffraction optical waveguide structure modulates light information through wavefront modulation for propagation within the optical waveguide and then reproduces the light information through further wavefront modulation, thus achieving optical information transmission. Analysis indicates that the theoretical maximum field of view can reach 90° × 90°. With an actual field of view set to 53° × 53°, an entrance pupil size of 3.2 × 3.2 mm², an eye relief of 10 mm, and 50 pupil expansion, the system’s total energy transmission efficiency is 37%, with field of view uniformity at 91% and uniformity within the eye movement range reaching 97%.

Abstract Background This study aimed to quantitatively evaluate the left ventricular global and regional myocardial work of patients in Fabry disease (FD) by echocardiographic pressure–strain loop (PSL) analysis. Results The study included 48 patients with FD and 48 healthy controls matched for age and sex. According to the presence/absence of left ventricular hypertrophy (LVH), the patients with FD were divided into an LVH + group and an LVH– group. Left ventricular blood pressure was estimated noninvasively according to echocardiographic valvular events and systolic pressure in the brachial artery. Left ventricular myocardial work parameters were acquired by echocardiographic pressure–strain loop analysis. The FD groups had a significantly lower global longitudinal strain (GLS), global work index, global work efficiency (GWE), global constructive work and higher global waste work than the control group (P

The influences of biological, chemical, and flow processes on soil structure through microbially induced carbonate precipitation (MICP) are not yet fully understood. In this study, we use a multi-level thresholding segmentation algorithm, genetic algorithm (GA) enhanced Kapur entropy (KE) (GAE-KE), to accomplish quantitative characterization of sandy soil structure altered by MICP cementation. A sandy soil sample was treated using MICP method and scanned by the synchrotron radiation (SR) micro-CT with a resolution of 6.5 μm. After validation, tri-level thresholding segmentation using GAE-KE successfully separated the precipitated calcium carbonate crystals from sand particles and pores. The spatial distributions of porosity, pore structure parameters, and flow characteristics were calculated for quantitative characterization. The results offer pore-scale insights into the MICP treatment effect, and the quantitative understanding confirms the feasibility of the GAE-KE multi-level thresholding segmentation algorithm.

Abstract Purpose This study aimed to report a newly developed, high‐fidelity synthetic simulator to simulate excision and primary anastomotic (EPA) bulbar urethroplasty and its clinical use for new practitioners in shortening the learning curve. Material and Methods The bulbar urethral anastomosis simulator consists of several standardized components created according to the actual size of the male patient. Interns, novice residents, and fellows inexperienced with urethral reconstruction (n = 10, 5, 5) from different medical centres were invited to participate in the training programme. Two reconstructive urology experts monitored each practice. Following the training, three kinds of validity testing were used to assess the simulator: face, content, and construct. In the intern group, the task performance in the first five training sessions and the last five training ones were compared using a self‐control approach. In the resident and fellow group, the real surgical data, including estimated blood loss, operative duration, and 6‐month post‐operative success rate of trainees after training, are plotted, which are compared with that of reconstructive urology experts (n = 5) included retrospectively to study the effectiveness of the simulator in shortening the learning curve. Results The overall mean satisfaction rate for the simulators was inspiring and evaluated by experts. In the intern group, significant improvement can be achieved through 10 training sessions (p

Abstract Purpose This study aimed to assess the safety and efficacy of percutaneous transhepatic cholangiography drainage (PTCD) and endoscopic retrograde cholangiopancreatography (ERCP) in palliative drainage and preoperative biliary drainage for treating malignant obstructive jaundice (MOJ). Methods A total of 520 patients with MOJ who underwent PTCD or ERCP were enrolled and classified into palliative drainage group and preoperative biliary drainage group. Baseline characteristics, liver function, blood routine, complications were compared among the groups. Results The technical success rates for PTCD and ERCP in palliative group were 97.1% and 85.9%. In palliative drainage group, PTCD had higher levels of total bilirubin (TB) reduction (53.0 (30.0,97.0) vs. 36.8 (17.9,65.0), p

Abstract Background Carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) caused infections of high mortality and brought a serious impact on public health. This study aims to evaluate the epidemiology, resistance and virulence characteristics of CR-hvKP and to identify potential drivers of cross-regional transmission in different regions of China, in order to provide a basis for developing targeted prevention measures. Methods Clinical K. pneumoniae strains were collected from Jiujiang and Nanchang in Jiangxi province between November 2021 to June 2022. Clinical data of patients (age, sex, source of infection, and diagnosis) were also gathered. We characterized these strains for their genetic relatedness using PFGE, antimicrobial and virulence plasmid structures using whole-genome sequencing, and toxicity using Galleria mellonella infection model. Results Among 609 strains, 45 (7.4%) CR-hvKP were identified, while the strains. isolated from Nanchang and Jiujiang accounted for 10.05% (36/358) and 3.59% (9/251). We observed that ST11-KL64 CR-hvKP had an overwhelming epidemic dominance in these two regions. Significant genetic diversity was identified among all ST11-KL64 CR-hvKP cross-regional transmission between Nanchang and Jiujiang and this diversity served as the primary driver of the dissemination of clonal groups. Virulence genes profile revealed that ST11-KL64 CR-hvKP might harbour incomplete pLVPK-like plasmids and primarily evolved from CRKP by acquiring the hypervirulence plasmid. We found the predominance of truncated-IncFIB/IncHI1B type virulence plasmids with a 25 kb fragment deletion that encoded iroBCDN clusters. Conclusion ST11-KL64 is the most cross-regional prevalent type CR-hvKPs in Jiangxi province, which mainly evolved from CRKPs by acquiring a truncated-IncHI1B/IncFIB virulence plasmid with the deletion of iroBCDN. Stricter surveillance and control measures are urgently needed to prevent the epidemic transmission of ST11-KL64 CR-hvKP.

Abstract Background To compare and analyze clinical characteristics of patients undergoing two surgeries and multiple surgeries and explore relevant factors to lay the foundation for clinical prediction. Methods A retrospective analysis was conducted on clinical data from all patients who underwent twice and multiple strabismus surgeries at Tianjin Eye Hospital between October 2012 and September 2021. Patients were divided into Group A (two surgeries) and Group B (more than two surgeries) based on the cumulative number of surgeries performed. Clinical details at the first recurrence, including sex, age, native place, overall medical history, onset time, visual acuity, affected muscle(s), etc., were documented. Non-parametric tests and chi-square tests were used to analyze clinical characteristics in each group. Binary and ordered logistic regression analysis assessed parameters associated with multiple reoperations. A linear mixed-term model observed factors impacting affected muscle(s) during surgery. Researchers examined clinical traits related to secondary strabismus variables. Results Among the 910 included patients, 840 required two surgeries (Group A) and 70 underwent more than two surgeries (Group B). Significant differences were found in age, onset time, interval time, and secondary factors. Regression analysis highlighted the significant impact of interval time on the reoperation rate, effectively predicting outcomes in patients with concomitant strabismus. Other ophthalmoplegia and secondary factors significantly influenced reoperation rates in patients with non-concomitant strabismus. Interval time, esotropia, and exotropia were linked to concomitant secondary strabismus patients, while the number of surgeries, DVD, esotropia, exotropia, and esotropia V-pattern were associated with non-concomitant secondary strabismus patients. In a longitudinal study, patients with multiple surgeries showed a correlation between the vertical deviation angle magnitude and the number of involved extraocular muscles. Regression analysis revealed that in patients with concomitant strabismus, interval time, exotropia, and esotropia influenced the total number of muscles during surgery. For patients with non-concomitant strabismus, interval time, secondary factors, and SOP impacted the total number of muscles during surgery. Conclusions Interval time in patients with concomitant strabismus, as well as secondary and other ophthalmoplegia in non-concomitant strabismus, are the main factors for multiple reoperations.

Abstract Background Plastids originated from an ancient endosymbiotic event and evolved into the photosynthetic organelles in plant cells. They absorb light energy and carbon dioxide, converting them into chemical energy and oxygen, which are crucial for plant development and adaptation. However, little is known about the plastid genome to light adaptation. Petrocosmea, a member of the Gesneriaceae family, comprises approximately 70 species with diverse light environment, serve as an ideal subject for studying plastomes adapt to light. Results In this study, we selected ten representative species of Petrocosmea from diverse light environments, assembled their plastid genomes, and conducted a comparative genomic analysis. We found that the plastid genome of Petrocosmea is highly conserved in both structure and gene content. The phylogenetic relationships reconstructed based on the plastid genes were divided into five clades, which is consistent with the results of previous studies. The vast majority of plastid protein-coding genes were under purifying selection, with only the rps8 and rps16 genes identified under positive selection in different light environments. Notably, significant differences of evolutionary rate were observed in NADH dehydrogenase, ATPase ribosome, and RNA polymerase between Clade A and the other clades. Additionally, we identified ycf1 and several intergenic regions (trnH-psbA, trnK-rps16, rpoB-trnC, petA-psbJ, ccsA-trnL, rps16-trnQ, and trnS-trnG) as candidate barcodes for this emerging ornamental horticulture. Conclusion We newly assembled ten plastid genomes of Petrocosmea and identified several hypervariable regions, providing genetic resources and candidate markers for this promising emerging ornamental horticulture. Furthermore, our study suggested that rps8 and rps16 were under positive selection and that the evolutionary patterns of NADH dehydrogenase, ATPase ribosome, and RNA polymerase were related to the diversity light environment in Petrocosmea. This revealed an evolutionary scenario for light adaptation of the plastid genome in plants.

Abstract Background Individuals who have experienced severe traumatic events are estimated to have a post-traumatic stress disorder (PTSD) prevalence rate ranging from 10 to 50%, while those not affected by trauma exposure are often considered to possess psychological resilience. However, the neural mechanisms underlying the development of PTSD, especially resilience after trauma, remain unclear. This study aims to investigate changes of cortical morphometric similarity network (MSN) in PTSD and trauma-exposed healthy individuals (TEHI), as well as the associated molecular alterations in gene expression, providing potential targets for the prevention and intervention of PTSD. Methods We recruited PTSD patients and TEHI who had experienced severe earthquakes, and healthy controls who had not experienced earthquakes. We identified alterations in the whole-brain MSN changes in PTSD and TEHI, and established associations between these changes and brain-wide gene expression patterns from the Allen Human Brain Atlas microarray dataset using partial least squares regression. Results At the neuroimaging level, we found not only trauma-susceptible changes in TEHI same as those in PTSD, but also unique neurobiological alterations to counteract the deleterious impact of severe trauma. We identified 1444 and 2214 genes transcriptionally related to MSN changes in PTSD and TEHI, respectively. Functional enrichment analysis of weighted gene expression for PTSD and TEHI revealed distinct enrichments in Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, gene expression profiles of astrocytes, excitatory neurons, and microglial cells are highly related to MSN abnormalities in PTSD. Conclusions The formation of resilience may be by an active compensatory process of the brain. The combination of macroscopic neuroimaging changes and microscopic human brain transcriptomics could offer a more direct and in-depth understanding of the pathogenesis of PTSD and psychological resilience, shedding light on new targets for the prevention and treatment of PTSD.

Abstract Background Migraine is a prevalent neurologic disorder that affects women more than men. Examining health-related quality of life (HRQoL) by gender can aid decision makers in prioritizing future treatment and prevention programs. We aimed to quantify HRQoL by different levels of migraine disability and by gender. Methods As part of a Canada-wide cross-sectional study, we administered an online survey to employed adults who self-reported a diagnosis of migraine. Migraine disability level was assessed using the Migraine Disability Assessment questionnaire (MIDAS). MIDAS scores were used to categorize respondents as having little to no, mild, moderate, or severe level of migraine-related disability. Physical and mental component summary scores (PCS and MCS) and health utilities were derived from responses to the Veterans Rand 12 Item Health Survey. PCS, MCS, and health utilities were summarized by migraine-related disability levels and gender. Covariate-adjusted linear regressions were used to examine the association between migraine disability level and health utility by gender. Results A total of 441 participants completed the survey. The sample was predominantly women (60.1%), White race (75.5%), and had a mean age of 37 years. Mean health utility, PCS, and MCS scores were 0.61 (0.22), 45.0 (7.7), and 43.4 (11.0), respectively. All three scores decreased with increased migraine disability level. Gender differences on HRQoL within each migraine disability level were not statistically significant, except in the little to no disability level where women had lower mean MCS scores and health utility relative to men [mean (SD) MCS: women 44.0 (11.3); men 55.1 (8.1), p

Abstract Background Muscle-invasive bladder carcinoma (MIBC) is a serious and more advanced stage of bladder carcinoma. N6-Methyladenosine (m6A) is a dynamic and reversible modifications that primarily affects RNA stability and alternative splicing. The dysregulation of m6A in MIBC can be potential target for clinical interventions, but there have been limited studies on m6A modifications in MIBC and their associations with post-transcriptional regulatory processes. Methods Paired tumor and adjacent-normal tissues were obtained from three patients with MIBC following radical cystectomy. The additional paired tissues for validation were obtained from patients underwent transurethral resection. Utilizing Nanopore direct-RNA sequencing, we characterized the m6A RNA methylation landscape in MIBC, with a focus on identifying post-transcriptional events potentially affected by changes in m6A sites. This included an examination of differential transcript usage, polyadenylation signal sites, and variations in poly(A) tail length, providing insights into the broader impact of m6A alterations on RNA processing in MIBC. Results The prognostic-related m6A genes and m6A-risk model constructed by machine learning enables the stratification of high and low-risk patients with precision. A novel m6A modification site in the 3’ untranslated region (3’UTR) of IGLL5 gene were identified, characterized by a lower m6A methylation ratio, elongated poly(A) tails, and a notable bias in transcript usage. Furthermore, we discovered two particular transcripts, VWA1-203 and CEBPB-201. VWA1-203 displayed diminished m6A methylation levels, a truncated 3’UTR, and an elongated poly(A) tail, whereas CEBPB-201 showed opposite trends, highlighting the complex interplay between m6A modifications and RNA processing. Source code was provided on GitHub ( https://github.com/lelelililele/Nanopore-m6A-analysis ). Conclusions The state-of-the-art Nanopore direct-RNA sequencing and machine learning techniques enables comprehensive identification of m6A modification and provided insights into the potential post-transcriptional regulation mechanisms on the development and progression in MIBC.

Abstract We investigated fasting hypertriglyceridemia as predictors of all‐cause, cardiovascular, and non‐cardiovascular mortality in an elderly male Chinese population, while accounting for various conventional cardiovascular risk factors. Our participants were elderly men recruited from residents living in a suburban town of Shanghai (≥60 years of age, n = 1583). Hypertriglyceridemia was defined as a fasting serum triglycerides concentration ≥1.70 mmol/L. Subgroup analyses were performed according to current smoking (yes vs. no), alcohol intake (yes vs. no), and the presence and absence of hypertension and hyperglycemia. During a median of 7.9 years follow‐up, all‐cause, cardiovascular, and non‐cardiovascular deaths occurred in 279, 112, and 167 participants, respectively. After adjustment for confounding factors, fasting hypertriglyceridemia was not significantly (p ≥ .33) associated with the risk of all‐cause, cardiovascular, and non‐cardiovascular mortality. However, there was significant (p = .03) interaction between hypertriglyceridemia and the presence and absence of hypertension in relation to all‐cause mortality. In normotensive, but not hypertensive individuals, hypertriglyceridemia was significantly associated with a higher risk of all‐cause mortality (hazard ratio 1.57, 95% confidence interval 1.06–2.31). In further non‐parametric analyses in normotensive individuals, the age‐standardized rate for all‐cause mortality increased from 18.9 in quartile 1 to 20.0, to 24.7, and to 39.9 per 1000 person‐years in quartiles 2, 3, and 4 of serum triglycerides concentration, respectively (ptrend = .0004). Similar results were observed for cardiovascular mortality. Our study in elderly male Chinese showed that fasting hypertriglyceridemia was associated with a higher risk of all‐cause and cardiovascular mortality in patients with normotension but not those with hypertension.

ABSTRACT: Due to its beneficial effects on human health, Bifidobacterium is commonly added to milk powder. Accurate quantification of viable Bifidobacterium is essential for assessing the therapeutic efficacy of milk powder. In this study, we introduced a novel propidium monoazide (PMA)-antibiotic fluorescence in situ hybridization (AFISH)-flow cytometry (FC) method to rapidly and accurately quantify viable Bifidobacterium cells in milk powder. Briefly, Bifidobacterium cells were treated with chloramphenicol (CM) to increase their rRNA content, followed by staining with RNA-binding oligonucleotide probes, based on the AFISH technique. Then, the DNA-binding dye PMA was used to differentiate between viable and nonviable cells. The PMA-AFISH-FC method, including sample pretreatment, CM treatment, dual staining, and FC analysis, required approximately 2 h and was found to be better than the current methods. This is the first study to implement FC combined with PMA and an oligonucleotide probe for detecting Bifidobacterium.

Background: No data exist on the efficacy and safety of anlotinib plus camrelizumab doublet as second-line therapy for advanced esophageal squamous cell carcinoma (ESCC). Although anlotinib and the programmed death-1 (PD-1) inhibitor camrelizumab are used as treatments for ESCC, the combined use of anlotinib and camrelizumab as a second-line therapy has not been reported. Therefore, this study explored the efficacy and toxicity of anlotinib plus camrelizumab as second-line therapy for advanced ESCC. Methods: Fifty-eight patients with advanced ESCC undergoing second-line therapy, either with anlotinib plus camrelizumab or anlotinib plus S-1, were enrolled and retrospectively analyzed at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2021. The primary endpoint was progression-free survival (PFS), with secondary endpoints including the objective response rate (ORR), disease control rate (DCR), and assessment of toxicity. Results: In patients with advanced ESCC, the anlotinib plus camrelizumab group (N = 32) exhibited longer PFS (8.00 vs. 4.53 months, P