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Abstract Background Human parainfluenza virus-1 (HPIV-1) is a notable pathogen instigating acute respiratory tract infections in children. The article is to elucidate the epidemiological and genetic characteristics of HPIV-1 circulating in Hangzhou during the period of 2021–2022. Methods A cohort of 2360 nasopharyngeal swabs were amassed and subsequently examined via RT-PCR, with HPIV-1 positive samples undergoing P gene sequencing. Results The highest HPIV-1 infection rates were found in children aged between 3 and 6 years. A pronounced positive rate persisted through the latter half of 2021, with a notable decline observed in the initial half of 2022. All HPIV-1 strains could be clustered into 2 groups: Cluster 1, with strains similar to those found in Japan (LC764865, LC764864), and Cluster 2, with strains similar to the Beijing strain (MW575643). Conclusion In conclusion, our study contributes to the comprehensive data on the epidemiological and genetic characteristics of HPIV-1 in pediatric patients from Hangzhou, post the COVID-19 peak.

Mesembryanthemum cordifolium, a perennial plant with crassulacean acid metabolism (CAM) in the Aizoaceae family, has significant ornamental and medicinal values. In this study, we reported the first complete chloroplast genome sequence of this species. The total genome size was 153,734 bp in length, including a large single-copy (LSC) region of 85,692 bp, a small single-copy (SSC) region of 18,212 bp, and a pair of inverted repeat (IR) regions of 24,915 bp by each. The overall GC content of the M. cordifolium chloroplast genome was 37.08%. The genome encodes 131 genes, comprising 87 protein-coding genes (PCGs), 36 transfer RNA genes (tRNAs), and eight ribosomal RNA genes (rRNAs). Phylogenetic analysis shows this species was relatively close to M. crystallinum. This chloroplast genome sequence will be valuable for species discrimination and for understanding phylogenetic relationships within the genus Mesembryanthemum.

This study examines the microstructural evolution, elemental distribution, phase composition, and hardness variations in multi-material samples fabricated using Laser Powder Bed Fusion (LPBF) with Invar and Ti6Al4V with compositional gradients mediated by copper. A range of compositional transitions from Invar to Ti6Al4V with different copper fractions are reported. Defects such as gas and keyhole pores were detected in well-deep keyhole mode areas, while lack of fusion defects were observed in samples with pure Cu interlayers due to poor wettability and processing parameter variations. Crack formation between interlayer gradient zones and Invar regions was linked to FeNi and CuNi intermetallic phases. Intermetallic compounds (e.g., FeNi, CuNi, TiFe, TiNi) significantly influenced the microstructure and mechanical performance. Vickers hardness testing shows varying hardness across different builds, with the highest hardness being observed in the gradient zone enabled by pure copper (approximately 620 HV). This study also underscores the need for tailored component design linking build processing parameters and compositional transitions in multi-material LPBF to achieve desired properties and component structural behaviour.

Optical imaging in the second near-infrared (NIR-II; 900–1880 nm) window is currently a popular research topic in the field of biomedical imaging. This study aimed to explore the application value of NIR-II fluorescence imaging in foot and ankle surgeries. A lab-established NIR-II fluorescence surgical navigation system was developed and used to navigate foot and ankle surgeries which enabled obtaining more high-spatial-frequency information and a higher signal-to-background ratio (SBR) in NIR-II fluorescence images compared to NIR-I fluorescence images; our result demonstrates that NIR-II imaging could provide higher-contrast and larger-depth images to surgeons. Three types of clinical application scenarios (diabetic foot, calcaneal fracture, and lower extremity trauma) were included in this study. Using the NIR-II fluorescence imaging technique, we observed the ischemic region in the diabetic foot before morphological alterations, accurately determined the boundary of the ischemic region in the surgical incision, and fully assessed the blood supply condition of the flap. NIR-II fluorescence imaging can help surgeons precisely judge surgical margins, detect ischemic lesions early, and dynamically trace the perfusion process. We believe that portable and reliable NIR-II fluorescence imaging equipment and additional functional fluorescent probes can play crucial roles in precision surgery.

Abstract Objectives Accurate segmentation of focal cortical dysplasia (FCD) lesions from MR images plays an important role in surgical planning and decision but is still challenging for radiologists and clinicians. In this study, we introduce a novel transformer-based model, designed for the end-to-end segmentation of FCD lesions from multi-channel MR images. Methods The core innovation of our proposed model is the integration of a convolutional neural network-based encoder-decoder structure with a multiscale transformer to augment the feature representation of lesions in the global field of view. Transformer pathways, composed of memory- and computation-efficient dual-self-attention modules, leverage feature maps from varying depths of the encoder to discern long-range interdependencies among feature positions and channels, thereby emphasizing areas and channels relevant to lesions. The proposed model was trained and evaluated on a public-open dataset including MR images of 85 patients using both subject-level and voxel-level metrics. Results Experimental results indicate that our model offers superior performance both quantitatively and qualitatively. It successfully identified lesions in 82.4% of patients, with a low false-positive lesion cluster rate of 0.176 ± 0.381 per patient. Furthermore, the model achieved an average Dice coefficient of 0.410 ± 0.288, outperforming five established methods. Conclusion Integration of the transformer could enhance the feature presentation and segmentation performance of FCD lesions. The proposed model has the potential to serve as a valuable assistive tool for physicians, enabling rapid and accurate identification of FCD lesions. The source code and pre-trained model weights are available at https://github.com/zhangxd0530/MS-DSA-NET . Critical relevance statement This multiscale transformer-based model performs segmentation of focal cortical dysplasia lesions, aiming to help radiologists and clinicians make accurate and efficient preoperative evaluations of focal cortical dysplasia patients from MR images. Key Points The first transformer-based model was built to explore focal cortical dysplasia lesion segmentation. Integration of global and local features enhances the segmentation performance of lesions. A valuable benchmark for model development and comparative analyses was provided. Graphical Abstract

Abstract Shade avoidance helps plants maximize their access to light for growth under crowding. It is unknown, however, whether a priming shade avoidance mechanism exists that allows plants to respond more effectively to successive shade conditions. Here, we show that the shade-intolerant plant Arabidopsis can remember a first experienced shade event and respond more efficiently to the next event on hypocotyl elongation. The transcriptional regulator PHYTOCHROME-INTERACTING FACTOR 7 (PIF7) and the histone H3K27-demethylase RELATIVE OF EARLY FLOWERING 6 (REF6) are identified as being required for this shade avoidance memory. RNA-sequencing analysis reveals that shade induction of shade-memory-related genes is impaired in the pif7 and ref6 mutants. Based on the analyses of enrichments of H3K27me3, REF6 and PIF7, we find that priming shade treatment induces PIF7 accumulation, which further recruits REF6 to demethylate H3K27me3 on the chromatin of certain shade-memory-related genes, leading to a state poised for their transcription. Upon a second shade treatment, enhanced shade-mediated inductions of these genes result in stronger hypocotyl growth responses. We conclude that the transcriptional memory mediated by epigenetic modification plays a key role in the ability of primed plants to remember previously experienced shade and acquire enhanced responses to recurring shade conditions.

Lilium saccatum is a species of ornamental plant found in southeastern Xizang, China. In the present study, the complete chloroplast (cp) genome of L. saccatum was sequenced using next-generation sequencing (NGS). The de novo assembled cp genome was 151,839 bp in length, including a pair of inverted repeat regions (IRs; 26,421 bp), a small single-copy region (SSC; 17,528 bp), and a large single-copy region (LSC; 81,469 bp). The cp genome encodes 113 unique genes, including 79 protein-coding genes (PCGs), 30 tRNA genes, and four rRNA genes. The total GC content of the cp genome was 37.0%. Phylogenetic analysis of 24 cp genomes revealed that L. saccatum was closely related to L. souliei. This study could provide fundamental information for the phylogenomics and utilization of Lilium.

Automated pavement condition survey is of critical importance to road network management. There are three primary tasks involved in pavement condition surveys, namely data collection, data processing and condition evaluation. Artificial intelligence (AI) has achieved many breakthroughs in almost every aspect of modern technology over the past decade, and undoubtedly offers a more robust approach to automated pavement condition survey. This article aims to provide a comprehensive review on data collection systems, data processing algorithms and condition evaluation methods proposed between 2010 and 2023 for intelligent pavement condition survey. In particular, the data collection system includes AI-driven hardware devices and automated pavement data collection vehicles. The AI-driven hardware devices including right-of-way (ROW) cameras, ground penetrating radar (GPR) devices, light detection and ranging (LiDAR) devices, and advanced laser imaging systems, etc. These different hardware components can be selectively mounted on a vehicle to simultaneously collect multimedia information about the pavement. In addition, this article pays close attention to the application of artificial intelligence methods in detecting pavement distresses, measuring pavement roughness, identifying pavement rutting, analyzing skid resistance and evaluating structural strength of pavements. Based upon the analysis of a variety of the state-of-the-art artificial intelligence methodologies, remaining challenges and future needs with respect to intelligent pavement condition survey are discussed eventually.

Abstract Background In 2022, our team launched the pioneering national proficiency testing (PT) scheme for the pathological diagnosis of breast cancer, rapidly establishing its credibility throughout China. Aiming to continuously monitor and improve the proficiency of Chinese pathologists in breast pathology, the second round of the PT scheme was initiated in 2023, which will expand the number of participating institutions, and will conduct a nationwide investigation into the interpretation of HER2 0, 1+, and 2+/FISH- categories in China. Methods The methodology employed in the current round of PT scheme closely mirrors that of the preceding cycle in 2022, which is designed and implemented according to the “Conformity assessment—General requirements for proficiency testing”(GB/T27043—2012/ISO/IEC 17043:2010). More importantly, we utilized a statistics-based method to generate assigned values to enhance their robustness and credibility. Results The final PT results, published on the website of the National Quality Control Center for Cancer ( http://117.133.40.88:3927 ), showed that all participants passed the testing. However, a few institutions demonstrated systemic biases in scoring HER2 0, 1+, and 2+/FISH- with accuracy levels below 59%, considered unsatisfactory. Especially, the concordance rate for HER2 0 cases was only 78.1%, indicating challenges in distinguishing HER2 0 from low HER2 expression. Meanwhile, areas for histologic type and grade interpretation improvement were also noted. Conclusions Our PT scheme demonstrated high proficiency in diagnosing breast cancer in China. But it also identified systemic biases in scoring HER2 0, 1+, and 2+/FISH- at some institutions. More importantly, our study highlighted challenges in the evaluation at the extreme lower end of the HER2 staining spectrum, a crucial area for further research. Meanwhile, it also revealed the need for improvements in interpreting histologic types and grades. These findings strengthened the importance of robust quality assurance mechanisms, like the nationwide PT scheme conducted in this study, to maintain high diagnostic standards and identify areas requiring further training and enhancement.

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. Numerous recent studies report the potential of wireless electronic system for nerve defects repair. Unfortunately, few has met clinical needs for inadequate electrode precision, poor nerve entrapment and insufficient bioactivity of the matrix material. Herein, we present an advanced wireless electrical nerve stimulator, based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.

Abstract Hybrid immunity against SARS-CoV-2 has not been well studied in pregnancy. We conducted a comprehensive analysis of neutralizing antibodies (nAb) and binding antibodies in pregnant individuals who received mRNA vaccination, natural infection, or both. A third vaccine dose augmented nAb levels compared to the two-dose regimen or natural infection alone; this effect was more pronounced in hybrid immunity. There was reduced anti-Omicron nAb, but the maternal-fetal transfer efficiency remained comparable to that of other variants. Vaccine-induced nAbs were transferred more efficiently than infection-induced nAbs. Anti-spike receptor binding domain (RBD) IgG was associated with nAb against wild-type (Wuhan-Hu-1) following breakthrough infection. Both vaccination and infection-induced anti-RBD IgA, which was more durable than anti-nucleocapsid IgA. IgA response was attenuated in pregnancy compared to non-pregnant controls. These data provide additional evidence of augmentation of humoral immune responses in hybrid immunity in pregnancy.

Abstract Human enteroviruses are highly prevalent world-wide. Up to more than 100 subtypes of enteroviruses can cause several diseases, including encephalitis, meningitis, myocarditis, hand-foot-mouth disease, conjunctivitis, respiratory diseases, and gastrointestinal diseases, thus posing a great threat to human health. This study aimed to investigate the epidemiological characteristics of enterovirus in children in Hangzhou, China before and after the COVID-19 outbreak. Systematic monitoring of enterovirus infections was performed by collecting samples from the children admitted to the inpatient wards and outpatient departments in the Children’s Hospital, Zhejiang University School of Medicine, between January 2019 and May 2023. A commercial real-time RT PCR kit was utilized to detect enteroviruses. Among the 34,152 samples collected, 1162 samples, accounting for 3.4% of the samples, were tested positive for enteroviruses. The annual positive rates of the enteroviruses were 5.46%, 1.15%, 4.43%, 1.62%, and 1.96% in 2019, 2020, 2021, 2022, and May 2023, respectively. The positivity rate of the enteroviruses was highest among children aged 3–5 years and 5–7 years. Moreover, the monthly positivity rate of enterovirus infection ranged from 0.32% to 10.38%, with a peak in June and July. Serotypes, especially EV71 and CA16, causing severe symptoms such as HFMD, were decreasing, while the proportion of unidentified serotypes was on the rise. The incidence of enteroviruses in Hangzhou was higher in children aged 1–3 years and 7–18 years.

Objective Summarize the clinical and genetic characteristics of atypical Rett syndrome and developmental epileptic encephalopathy caused by IQSEC2 gene variation. Methods and Results From May 2020 to April 2022, Anhui Provincial Children's Hospital diagnosed and treated 4 children with atypical Rett syndrome and developmental epileptic encephalopathy caused by IQSEC2 gene variation, including 2 males and 2 females were a pair of identical twins. They all had comprehensive developmental delay before onset. At the age of 2 years, all cases gradually exhibited clinical manifestations of atypical Rett syndrome, such as frequent clapping, biting, sleep disorders (increased sleep or difficulty falling asleep), and grinding teeth, followed by developmental regression and seizures. The initial age of epilepsy was from 2 years and 2 months to 2 years and 10 months. All cases started with generalized tonic-clonic seizure, with epileptic spasm occurring between 2 and 11 months of course. Case 2, Case 3 and Case 4 were also accompanied by focal seizures. Four cases with VEEG background of 4-6 Hz θ wave, the VEEG during the interictal phase was a broad multifocal sharp slow complex wave. In Case 2, Case 3 and Case 4,MRI was abnormal, mainly with increased depth of cerebral hemispheric sulcus and gyrus. The whole exome sequencing suggested pathogenicity and possible pathogenic variations in the IQSEC2 gene, Case 1 and Case 2 were frameshift mutations of c. 608dup (p. Gln204Profs*35), while Case 3 and Case 4 were nonsense mutations of c.2231C > A (p.Ser744Ter) and c.2521C > T (p.Gln841Ter), respectively. The four mutation sites have not been reported domestically or internationally. All cases received treatment with multiple antiepileptic seizure medicine. The last follow-up age was from 4 years and 3 months to 6 years and 3 months. All cases were unable to walk alone and had no active language. There were no seizures in Case 1 for 3 years, occasional seizures in Case 2 and Case 4, and frequent seizures in Case 3. Conclusions IQSEC2 gene variation can manifest as atypical Rett syndrome, which can be accompanied by refractory epileptic spasms. Both males and females have severe phenotypes, and the severity of clinical phenotypes at the same mutation site varies. Our report enriches the variation spectrum and clinical phenotype spectrum of the IQSEC2 gene, expands the genetic spectrum of Rett syndrome and developmental epileptic encephalopathy, and provides value for the clinical diagnosis, treatment and subsequent research of this disease.

Abstract. Interpreting genes of interest is essential for identifying molecular mechanisms, but acquiring such information typically involves tedious manual retrieval. To streamline this process, the fanyi package offers tools to retrieve gene information from sources like National Center for Biotechnology Information (NCBI), significantly enhancing accessibility. Additionally, understanding the latest research advancements and sharing achievements are crucial for junior researchers. However, language barriers often restrict knowledge absorption and career development. To address these challenges, we developed the fanyi package, which leverages artificial intelligence (AI)-driven online translation services to accurately translate among multiple languages. This dual functionality allows researchers to quickly capture and comprehend information, promotes a multilingual environment, and fosters innovation in academic community. Meanwhile, the translation functions are versatile and applicable beyond biomedicine research to other domains as well. The fanyi package is freely available at https://github.com/YuLab-SMU/fanyi.

Abstract Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have been shown to promote angiogenesis after ischemic stroke, in which microRNAs (miRs) are believed to play an important role in exosome-mediated therapeutic effects, though the mechanism is still not clear. In this study, a series of molecular biological and cellular assays, both in vitro and in vivo, were performed to elucidate the role of exosomal miR-486 in angiogenesis following cerebral ischemic and its molecular mechanisms. Our results revealed that BMSC-Exos significantly improved neurological function and increased microvessel density in ischemic stroke rats. In vitro assays showed that BMSC-Exos promoted the proliferation, migration, and tube formation ability of oxygen–glucose deprivation/reoxygenation (OGD/R) injured rat brain microvascular endothelial cells (RBMECs). Importantly, BMSC-Exos increased the expression of miR-486 and phosphorylated protein kinase B (p-Akt) and down-regulated the protein level of phosphatase and tensin homolog (PTEN) in vivo and in vitro. Mechanistic studies demonstrated that transfection with miR-486 mimic enhanced RBMECs angiogenesis and increased p-Akt expression, while inhibited PTEN expression. On the other hand, the miR-486 inhibitor induced an opposite effect, which could be blocked by PTEN siRNA. It was thus concluded that exosomal miR-486 from BMSCs may enhance the functional recovery by promoting angiogenesis following cerebral ischemic injury, which might be related to its regulation of the PTEN/Akt pathway.

Abstract Background Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. Methods A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. Results This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p

Abstract Cross-linked polymers with covalent adaptable networks (CANs) can be reprocessed under external stimuli owing to the exchangeability of dynamic covalent bonds. Optimization of reprocessing conditions is critical since increasing the reprocessing temperature costs more energy and even deteriorates the materials, while reducing the reprocessing temperature via molecular design usually narrows the service temperature range. Exploiting CO2 gas as an external trigger for lowering the reprocessing barrier shows great promise in low sample contamination and environmental friendliness. Herein, we develop a type of CANs incorporated with ionic clusters that achieve CO2-facilitated recyclability without sacrificing performance. The presence of CO2 can facilitate the rearrangement of ionic clusters, thus promoting the exchange of dynamic bonds. The effective stress relaxation and network rearrangement enable the system with rapid recycling under CO2 while retaining excellent mechanical performance in working conditions. This work opens avenues to design recyclable polymer materials with tunable dynamics and responsive recyclability.

Abstract Background This study was designed to develop a combined radiomics nomogram to preoperatively predict the risk categorization of thymomas based on contrast-enhanced computed tomography (CE-CT) images. Materials The clinical and CT data of 178 patients with thymoma (100 patients with low-risk thymomas and 78 patients with high-risk thymomas) collected in our hospital from March 2018 to July 2023 were retrospectively analyzed. The patients were randomly divided into a training set (n = 125) and a validation set (n = 53) in a 7:3 ratio. Qualitative radiological features were recorded, including (a) tumor diameter, (b) location, (c) shape, (d) capsule integrity, (e) calcification, (f) necrosis, (g) fatty infiltration, (h) lymphadenopathy, and (i) enhanced CT value. Radiomics features were extracted from each CE-CT volume of interest (VOI), and the least absolute shrinkage and selection operator (LASSO) algorithm was performed to select the optimal discriminative ones. A combined radiomics nomogram was further established based on the clinical factors and radiomics scores. The differentiating efficacy was determined using receiver operating characteristic (ROC) analysis. Results Only one clinical factor (incomplete capsule) and seven radiomics features were found to be independent predictors and were used to establish the radiomics nomogram. In differentiating low-risk thymomas (types A, AB, and B1) from high-risk ones (types B2 and B3), the nomogram demonstrated better diagnostic efficacy than any single model, with the respective area under the curve (AUC), accuracy, sensitivity, and specificity of 0.974, 0.921, 0.962 and 0.900 in the training cohort, 0.960, 0.892, 0923 and 0.897 in the validation cohort, respectively. The calibration curve showed good agreement between the prediction probability and actual clinical findings. Conclusions The nomogram incorporating clinical factors and radiomics features provides additional value in differentiating the risk categorization of thymomas, which could potentially be useful in clinical practice for planning personalized treatment strategies.

Abstract Recent advancements in single-cell RNA sequencing (scRNAseq) have facilitated the discovery of previously unrecognized subtypes within prostate cancer (PCa), offering new insights into cancer heterogeneity and progression. In this study, we integrated scRNAseq data from multiple studies, comprising publicly available cohorts and data generated by our research team, and established the Human Prostate Single cell Atlas (HuPSA) and Mouse Prostate Single cell Atlas (MoPSA) datasets. Through comprehensive analysis, we identified two novel double-negative PCa populations: KRT7 cells characterized by elevated KRT7 expression and progenitor-like cells marked by SOX2 and FOXA2 expression, distinct from NEPCa, and displaying stem/progenitor features. Furthermore, HuPSA-based deconvolution re-classified human PCa specimens, validating the presence of these novel subtypes. We then developed a user-friendly web application, “HuPSA–MoPSA” ( https://pcatools.shinyapps.io/HuPSA-MoPSA/ ), for visualizing gene expression across all newly established datasets. Our study provides comprehensive tools for PCa research and uncovers novel cancer subtypes that can inform clinical diagnosis and treatment strategies.

In this paper, we use variational methods to prove the existence of a positive solution for the following class of logarithmic fractional Schrödinger–Poisson system: \begin{equation*} \begin{cases} \epsilon^{2s}\left(-\Delta\right)^{s} u+V(x)u-\phi(x)u= u \log {u^{2}}&\quad\text{ in }\mathbb{R}^{3}, \\ \epsilon^{2t}\left(-\Delta\right)^{t}\phi=|u|^{2}&\quad\text{ in }\mathbb{R}^{3}, \end{cases} \end{equation*} where $\epsilon>0$, $s,t\in(0,1)$, $\left(-\Delta\right)^{\alpha}$ is the fractional Laplacian and $V$ is a saddle-like potential.

Abstract Introduction To assess the safety and efficacy of repeated intravitreal injections of RC28-E, a novel bispecific antibody that simultaneously binds vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with neovascular age-related macular degeneration (AMD). This was a prospective, multicenter, open-label clinical trial; 37 patients with choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) letter scores between 73 and 34 were enrolled. Methods Treatment regimens consisted of a 3-month loading phase and a pro re nata (PRN) maintenance phase. This study included three treatment groups: the 0.5, 1.0, and 2.0 mg RC28-E groups, with escalating doses ranging from 0.5 to 2.0 mg. Patients were evaluated monthly for 48 weeks. Safety was assessed based on ocular and systemic adverse events (AEs), pharmacokinetic characteristics, and the presence of anti-RC28-E antibodies. Efficacy was assessed using the mean change in BCVA and central subfield thickness (CST) from baseline to week 48. Results Most AEs were mild or moderate. The most common AE was a minor injection-related subconjunctival hemorrhage (16.2%). The AEs did not increase with dose or repeated injections. At week 48, mean improvements in BCVA from baseline in the 0.5, 1.0, and 2.0 mg groups were 6.1 ± 8.3, 9.9 ± 10.7, and 7.6 ± 9.38 letters, respectively; mean reductions in CST in the three groups were 112.1 ± 160.5, 175.1 ± 212.4, and 128.7 ± 145.8 μm, respectively. The serum RC28-E concentrations in 95% of the patients were below the quantification limit of the assay. No significant change from baseline was observed in the mean plasma concentrations of VEGF or FGF over the 48 weeks of treatment. Pre-treatment antibodies to RC28-E were detected in 1 of the 37 patients. Antibodies to RC28-E were detected in two patients after dosing with RC28-E for 48 weeks. Conclusion RC28-E was well tolerated and exhibited an overall favorable safety profile with evidence of improvements in BCVA and anatomical parameters.

Abstract Parents of children with retinoblastoma, the most common primary ocular malignant tumour in childhood, bear a heavy caregiving burden and are very susceptible to fatigue. However, little is known about their current status of fatigue and factors influencing fatigue; therefore,this study, based on the theory of unpleasant symptoms, and included 317 parents of children with retinoblastoma in China, whose general demographic data were collected, and on whom the fatigue severity scale (FSS), the generalized anxiety disorder (GAD-7) and 2-item patient health questionnaire (PHQ-2) were administered, from 9 March to 1 June 2020. The parents’ FSS score and fatigue incidence were 4.41 ± 1.14 and 67.19%, respectively. The fatigue level was positively correlated with anxiety, depression, education, times of hospitalisations, and treatment types (r = 0.125–0.468, P

Abstract Objective To investigate how antiretroviral therapy (ART) regimens and body mass index (BMI) interact to affect triglyceride (TG) levels in people living with HIV (PLWH). Methods This research involved 451 men living with HIV for cross-sectional analysis, and 132 underwent follow-up assessments in 2021 and 2023. Multivariate logistic regression identified key factors, while covariance regression models assessed interactions between ART regimens and BMI on TG levels. Results The result of this cross-sectional study indicated that advanced AIDS (acquired immune deficiency syndrome) stage (OR = 2.756, P = 0.003), higher BMI (OR = 1.131, P = 0.003), and waist-hip ratio (WHR, OR = 44.684, P = 0.019) are closely associated with high triglyceride levels. Additionally, regimens containing zidovudine (AZT) (OR = 3.927, P

Abstract Background Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a novel subtype of renal cell carcinoma characterized by its relatively low incidence and indolent behavior. We report a rare case of ESC-RCC concurrent with clear cell renal cell carcinoma (ccRCC) in a single kidney. Case presentation A 48-year-old male, was found to have a mixed echogenic mass in the left kidney during a physical examination. He has no history of hematuria and flank pain. An abdominal CT scan revealed a 3.0 * 1.9 * 2.5 cm3 mass with unclearly bordered at the lower pole of the left kidney. Abdominal MRI showed two nodules of different sizes in the left kidney, suggesting the possibility of a tumor. The patient underwent a subtotal nephrectomy, and the postoperative pathological results indicated ESC-RCC combined with ccRCC. The patient recovered well without tumor recurrence during the 12-month follow-up. Conclusion We reported a case of renal composite tumors, comprising the rare ESC-RCC and the more common ccRCC. Imaging combined with postoperative pathological examination is crucial for the definitive diagnosis of these rare tumors.

Abstract Background Neoadjuvant therapy (NT) has increased survival rates for patients with locally advanced esophageal cancer (EC), but estimating the impact of NT treatment prior to surgery is still very difficult. Methods A retrospective study of the clinical information of 150 patients with locally advanced EC who got NT at Qilu Hospital of Shandong University between June 2018 and June 2023. Patients were randomized into training and internal validation groups at a 3:1 ratio. Furthermore, an external validation cohort comprised 38 patients who underwent neoadjuvant therapy at Qianfoshan Hospital in the Shandong Province between June 2021 and June 2023. Independent risk factors were identified using univariate and multivariate logistic regression (forward stepwise regression). Predictive models and dynamic web nomograms were developed by integrating these risk factors. Results A total of 188 patients with locally advanced EC were enrolled, of whom 118 achieved stage I of neoadjuvant pathologic TNM (ypTNM) after receiving NT and 129 achieved grades 0-1 in the tumor regression grade (TRG). Logistic regression analysis identified five independent predictors of TRG grades 0-1: pulmonary function tests (PFT), prognostic nutritional index (PNI), triglyceride (TG) levels, squamous cell carcinoma antigen (SCC-Ag) levels, and combination immunotherapy. The areas under the receiver operating characteristic (ROC) curves for the training, internal validation, and external validation groups were 0.87, 0.75, and 0.80, respectively. Meanwhile, two independent predictors of stage I of ypTNM were identified: prealbumin (PA) and SCC antigen. The areas under the ROC curves for the training, internal validation, and external validation groups were 0.78, 0.67, and 0.70, respectively. The Hosmer-Lemeshow test for both predictive models showed excellent calibration, with well-fitted calibration curves. Decision curve analysis (DCA) and clinical impact curves (CIC) have demonstrated that nomograms are of clinical utility. Conclusion The nomograms performed well in predicting the likelihood of stage I of ypTNM and TRG grade 0-1 after NT in patients with locally advanced EC. It helps thoracic surgeons to predict the sensitivity of patients to NT before surgery, which enables precise treatment of patients with locally advanced EC.

Abstract The calculation of electron density distribution using density functional theory (DFT) in materials and molecules is central to the study of their quantum and macro-scale properties, yet accurate and efficient calculation remains a long-standing challenge. We introduce ChargE3Net, an E(3)-equivariant graph neural network for predicting electron density in atomic systems. ChargE3Net enables the learning of higher-order equivariant features to achieve high predictive accuracy and model expressivity. We show that ChargE3Net exceeds the performance of prior work on diverse sets of molecules and materials. When trained on the massive dataset of over 100K materials in the Materials Project database, our model is able to capture the complexity and variability in the data, leading to a significant 26.7% reduction in self-consistent iterations when used to initialize DFT calculations on unseen materials. Furthermore, we show that non-self-consistent DFT calculations using our predicted charge densities yield near-DFT performance on electronic and thermodynamic property prediction at a fraction of the computational cost. Further analysis attributes the greater predictive accuracy to improved modeling of systems with high angular variations. These results illuminate a pathway towards a machine learning-accelerated ab initio calculations for materials discovery.

Abstract Anion exchanger 3 (AE3) is pivotal in regulating intracellular pH across excitable tissues, yet its structural intricacies and functional dynamics remain underexplored compared to other anion exchangers. This study unveils the structural insights into human AE3, including the cryo-electron microscopy structures for AE3 transmembrane domains (TMD) and a chimera combining AE3 N-terminal domain (NTD) with AE2 TMD (hAE3NTD2TMD). Our analyzes reveal a substrate binding site, an NTD-TMD interlock mechanism, and a preference for an outward-facing conformation. Unlike AE2, which has more robust acid-loading capabilities, AE3’s structure, including a less stable inward-facing conformation due to missing key NTD-TMD interactions, contributes to its moderated pH-modulating activity and increased sensitivity to the inhibitor DIDS. These structural differences underline AE3’s distinct functional roles in specific tissues and underscore the complex interplay between structural dynamics and functional specificity within the anion exchanger family, enhancing our understanding of the physiological and pathological roles of the anion exchanger family.

Abstract Dihydroorotase (DHOase) is the third enzyme in the six enzymatic reaction steps of the endogenous pyrimidine nucleotide de novo biosynthesis pathway, which is a metabolic pathway conserved in both bacteria and eukaryotes. However, research on the biological function of DHOase in plant pathogenic fungi is very limited. In this study, we identified and named MoPyr4, a homologous protein of Saccharomyces cerevisiae DHOase Ura4, in the rice blast fungus Magnaporthe oryzae and investigated its ability to regulate fungal growth, pathogenicity, and autophagy. Deletion of MoPYR4 led to defects in growth, conidiation, appressorium formation, the transfer and degradation of glycogen and lipid droplets, appressorium turgor accumulation, and invasive hypha expansion in M. oryzae, which eventually resulted in weakened fungal pathogenicity. Long-term replenishment of exogenous uridine-5’-phosphate (UMP) can effectively restore the phenotype and virulence of the ΔMopyr4 mutant. Further study revealed that MoPyr4 also participated in the regulation of the Pmk1-MAPK signaling pathway, co-localized with peroxisomes for the oxidative stress response, and was involved in the regulation of the Osm1-MAPK signaling pathway in response to hyperosmotic stress. In addition, MoPyr4 interacted with MoAtg5, the core protein involved in autophagy, and positively regulated autophagic degradation. Taken together, our results suggested that MoPyr4 for UMP biosynthesis was crucial for the development and pathogenicity of M. oryzae. We also revealed that MoPyr4 played an essential role in the external stress response and pathogenic mechanism through participation in the Pmk1-MAPK signaling pathway, peroxisome-related oxidative stress response mechanism, the Osm1-MAPK signaling pathway and the autophagy pathway.

Abstract Named entity recognition is a fundamental subtask for knowledge graph construction and question-answering in the agricultural diseases and pests field. Although several works have been done, the scarcity of the Chinese annotated dataset has restricted the development of agricultural diseases and pests named entity recognition(ADP-NER). To address the issues, a large-scale corpus for the Chinese ADP-NER task named AgCNER was first annotated. It mainly contains 13 categories, 206,992 entities, and 66,553 samples with 3,909,293 characters. Compared with other datasets, AgCNER maintains the best performance in terms of the number of categories, entities, samples, and characters. Moreover, this is the first publicly available corpus for the agricultural field. In addition, the agricultural language model AgBERT is also fine-tuned and released. Finally, the comprehensive experimental results showed that BiLSTM-CRF achieved F1-score of 93.58%, which would be further improved to 94.14% using BERT. The analysis from multiple aspects has verified the rationality of AgCNER and the effectiveness of AgBERT. The annotated corpus and fine-tuned language model are publicly available at https://doi.org/XXX and https://github.com/guojson/AgCNER.git .

Abstract Purpose There is mounting evidence that patients with liver cancer can benefit from Immune checkpoint inhibitors. However, due to the high cost and low efficacy, we aimed to explore new biomarkers for predicting the efficacy of immunotherapy. Methods Specimens and medical records of liver cancer patients treated at Drum Tower Hospital of Nanjing University were collected, and the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in tissues as well as the corresponding antibodies in serum were examined to find biomarkers related to the prognosis of immunotherapy and to explore its mechanism in the development of liver cancer. Results KK-LC-1 expression was found to be 34.4% in histopathological specimens from 131 patients and was significantly correlated with Foxp3 expression (P = 0.0356). The expression of Foxp3 in the tissues of 24 patients who received immunotherapy was significantly correlated with overall survival (OS) (P = 0.0247), and there was also a tendency for prolonged OS in patients with high expression of KK-LC-1. In addition, the expression of KK-LC-1 antibody in the serum of patients who received immunotherapy with a first efficacy evaluation of stable disease (SD) was significantly higher than those with partial response (PR) (P = 0.0413). Conclusions Expression of KK-LC-1 in both tissues and serum has been shown to correlate with the prognosis of patients treated with immunotherapy, and KK-LC-1 is a potential therapeutic target for oncological immunotherapy.

Abstract Cut vertices and cut edges are valuable for analyzing connectivity problems in classical graph theory. However, they cannot deal with certain fuzzy problems. In order to solve this problem, this paper introduces the definitions of fuzzy strong cut vertices and fuzzy strong cut edges, and characterizes fuzzy strong cut vertices and fuzzy strong cut edges in fuzzy trees, complete fuzzy graphs, and fuzzy cycles. Finally, practical applications verify the effectiveness of the theory in network stability analysis.

Abstract Ulcerative colitis (UC) is a chronic inflammatory bowel disease with intricate pathogenesis and varied presentation. Accurate diagnostic tools are imperative to detect and manage UC. This study sought to construct a robust diagnostic model using gene expression profiles and to identify key genes that differentiate UC patients from healthy controls. Gene expression profiles from eight cohorts, encompassing a total of 335 UC patients and 129 healthy controls, were analyzed. A total of 7530 gene sets were computed using the GSEA method. Subsequent batch correction, PCA plots, and intersection analysis identified crucial pathways and genes. Machine learning, incorporating 101 algorithm combinations, was employed to develop diagnostic models. Verification was done using four external cohorts, adding depth to the sample repertoire. Evaluation of immune cell infiltration was undertaken through single-sample GSEA. All statistical analyses were conducted using R (Version: 4.2.2), with significance set at a P value below 0.05. Employing the GSEA method, 7530 gene sets were computed. From this, 19 intersecting pathways were discerned to be consistently upregulated across all cohorts, which pertained to cell adhesion, development, metabolism, immune response, and protein regulation. This corresponded to 83 unique genes. Machine learning insights culminated in the LASSO regression model, which outperformed others with an average AUC of 0.942. This model's efficacy was further ratified across four external cohorts, with AUC values ranging from 0.694 to 0.873 and significant Kappa statistics indicating its predictive accuracy. The LASSO logistic regression model highlighted 13 genes, with LCN2, ASS1, and IRAK3 emerging as pivotal. Notably, LCN2 showcased significantly heightened expression in active UC patients compared to both non-active patients and healthy controls (P

Abstract Advancements in CRISPR technology, particularly the development of base editors, revolutionize genetic variant research. When combined with model organisms like zebrafish, base editors significantly accelerate and refine in vivo analysis of genetic variations. However, base editors are restricted by protospacer adjacent motif (PAM) sequences and specific editing windows, hindering their applicability to a broad spectrum of genetic variants. Additionally, base editors can introduce unintended mutations and often exhibit reduced efficiency in living organisms compared to cultured cell lines. Here, we engineer a suite of adenine base editors (ABEs) called ABE-Ultramax (Umax), demonstrating high editing efficiency and low rates of insertions and deletions (indels) in zebrafish. The ABE-Umax suite of editors includes ABEs with shifted, narrowed, or broadened editing windows, reduced bystander mutation frequency, and highly flexible PAM sequence requirements. These advancements have the potential to address previous challenges in disease modeling and advance gene therapy applications.

Abstract Background High doses of long-acting opioids were used to facilitate off-pump coronary artery bypass grafting procedure, which may result in opioid-related adverse events after surgery. Transcutaneous electrical acupoint stimulation (TEAS) had been reported to be effective in reducing intraoperative opioids consumption during surgery. The aim of this study is to assess whether TEAS with difference acupoints can reduce the doses of opioid analgesics. Methods This was a multicenter, randomized, controlled, double-blind trial. Patients underwent off-pump coronary artery bypass grafting under general anesthesia were enrolled. Eligible patients were randomly and equally grouped into sham acupuncture group (n = 105), regional acupoints combination group (n = 105), or distal–proximal acupoints combination group (n = 105) using a centralized computer-generated randomization system. Transcutaneous electrical acupoint stimulation was applied for 30 min before anesthesia induction. The primary outcome was the doses of sufentanil during anesthesia. Secondary outcomes included the highest postoperative vasoactive-inotropic scores within 24 h, intraoperative propofol consumption, length of mechanical ventilation, duration of cardiac care unit and postoperative hospital stay, incidence of postoperative complications, and mortality within 30 days after surgery. Results Of the 315 randomized patients, 313 completed the trial. In the modified intention-to-treat analysis, the doses of sufentanil were 303.9 (10.8) μg in the distal–proximal acupoints group, significantly lower than the sham group, and the mean difference was − 34.9 (− 64.9 to − 4.9) μg, p = 0.023. The consumption of sufentanil was lower in distal–proximal group than regional group (303.9 vs. 339.5), and mean difference was − 35.5 (− 65.6 to − 5.5) μg, p = 0.020. The distal–proximal group showed 10% reduction in opioids consumption comparing to both regional and sham groups. Secondary outcomes were comparable among three groups. Conclusion Transcutaneous electrical acupoint stimulation with distal–proximal acupoints combination, compared to regional acupoints combination and sham acupuncture, significantly reduced sufentanil consumption in patients who underwent off-pump coronary artery bypass grafting surgery.

Introduction: The aims of this study are to explore the factors affecting mild cognitive impairment in patients with chronic kidney disease (CKD) who are not undergoing dialysis and to construct and validate a nomogram risk prediction model. Methods: Using a convenience sampling method, 383 non-dialysis CKD patients from two tertiary hospitals in Chengdu were selected between February 2023 and August 2023 to form the modeling group. The patients were divided into a mild cognitive impairment group (n = 192) and a non-mild cognitive impairment group (n = 191), and factors such as demographics, disease data, and sleep disorders were compared between the two groups. Univariate and multivariate binary logistic regression analyses were used to identify independent influencing factors, followed by collinearity testing, and construction of the regression model. The final risk prediction model was presented through a nomogram and an online calculator, with internal validation using Bootstrap sampling. For external validation, 137 non-dialysis CKD patients from another tertiary hospital in Chengdu were selected between October 2023 and December 2023. Results: In the modeling group, 192 (50.1%) of the non-dialysis CKD patients developed mild cognitive impairment, and in the validation group, 56 (40.9%) patients developed mild cognitive impairment, totaling 248 (47.7%) of all sampled non-dialysis CKD patients. Age, educational level, Occupation status, Use of smartphone, sleep disorders, hemoglobin, and platelet count were independent factors influencing the occurrence of mild cognitive impairment in non-dialysis CKD patients (all p < 0.05). The model evaluation showed an area under the ROC curve of 0.928, 95% CI (0.902, 0.953) in the modeling group, and 0.897, 95% CI (0.844, 0.950) in the validation group. The model's Youden index was 0.707, with an optimal cutoff value of 0.494, sensitivity of 0.853, and specificity of 0.854, indicating good predictive performance; calibration curves, Hosmer-Lemeshow test, and clinical decision curves indicated good calibration and clinical benefit. Internal validation results showed a consistency index (C-index) of 0.928, 95% CI (0.902, 0.953). Conclusion: The risk prediction model developed in this study shows excellent performance, demonstrating significant predictive potential for early screening of mild cognitive impairment in non-dialysis CKD patients. The application of this model will provide a reference for healthcare professionals, helping them formulate more targeted intervention strategies to optimize patient treatment and management outcomes.

Engineered bacteria have shown great potential in cancer immunotherapy by dynamically releasing therapeutic payloads and inducing sustained antitumor immune response with the crosstalk of immune cells. In previous studies, FOLactis was designed, which could secret an encoded fusion protein of Fms-related tyrosine kinase 3 ligand and co-stimulator OX40 ligand, leading to remarkable tumor suppression and exerting an abscopal effect by intratumoral injection. However, it is difficult for intratumoral administration of FOLactis in solid tumors with firm texture or high internal pressure. For patients without lesions such as abdominal metastatic tumors and orthotopic gastric tumors, intratumoral injection is not feasible and peritumoral maybe a better choice. Herein, an engineered bacteria delivery system is constructed based on in situ temperature-sensitive poloxamer 407 hydrogels. Peritumoral injection of FOLactis/P407 results in a 5-fold increase in the proportion of activated DC cells and a more than 2-fold increase in the proportion of effective memory T cells (TEM), playing the role of artificial lymph island. Besides, administration of FOLactis/P407 significantly inhibits the growth of abdominal metastatic tumors and orthotopic gastric tumors, resulting in an extended survival time. Therefore, these findings demonstrate the delivery approach of engineered bacteria based on in situ hydrogel will promote the efficacy and universality of therapeutics.

Through the creation and characterization of novel poly (L-lactic acid) (PLLA)-based nanocomposites containing graphene oxide (GO), nanocrystalline hydroxyapatite (nano-HAP), and nickel oxide (NiO) nanoparticles, this study seeks to improve the performance of bone tissue scaffolds. Utilizing a casting procedure to create nanocomposites, wet chemical methods were used to synthesize nano-HAP. X-ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy were used to characterize the materials. The nanocomposite comprising 5 % GO + 5 % NiO + 10 % nano-HAP showed a 110 % increase in tensile modulus, a 38 % increase in extension, and a 29 % increase in load-bearing capacity compared to plain PLLA. The results showed a considerable increase in mechanical strength. On the surfaces of the nanocomposite, osteoblast adhesion and proliferation increased by 185 %, according to biological tests. Studies on degradation revealed regulated rates that matched bones' natural mending process while preserving a pH environment that was steady. According to these results, adding nanostructures to PLLA scaffolds improves their mechanical and biological properties considerably, which may lead to therapeutic uses in bone tissue engineering in the future.

Both the physical features and social functions of urban green spaces (UGSs) are crucially important to the ecological and social benefits of urban residents. Increasing attention has been focused on exploring how UGS social functions affect the ecological and social benefits of urban residents, but the social functional classification of UGSs has rarely been studied, and related efficient classification methods are urgently needed. Thus, a novel methodological framework for accurately mapping UGS social functional zones was proposed by integrating remote sensing images, crowd-sourced geospatial data (i.e. point of interest data, the OpenStreetMap road network, and Baidu Map boundary), and a deep learning algorithm. A sequence of combination experiments and ablation experiments were designed for performance validation and for quantifying the contributions of individual crowd-sourced geospatial data to UGS social functional classification. The results showed that the proposed methodological framework can precisely and effectively map UGS social functional zones and that all kinds of crowd-sourced geospatial data contributed to improving the accuracy of UGS social functional classification. This study can assist planners and government departments in the rapid monitoring, effective management, and scientific planning of UGS social functional zones by providing accurate data sources and an effective mapping tool.

Osteoid plays a crucial role in directing cell behavior and osteogenesis through its unique characteristics, including viscoelasticity and liquid crystal (LC) state. Thus, integrating osteoid-like features into 3D printing scaffolds proves to be a promising approach for personalized bone repair. Despite extensive research on viscoelasticity, the role of LC state in bone repair has been largely overlooked due to the scarcity of suitable LC materials. Moreover, the intricate interplay between LC state and viscoelasticity in osteogenesis remains poorly understood. Here, we developed innovative hydrogel scaffolds with osteoid-like LC state and viscoelasticity using digital light processing with a custom LC ink. By utilizing these LC scaffolds as 3D research models, we discovered that LC state mediates high protein clustering to expose accessible RGD motifs to trigger cell-protein interactions and osteogenic differentiation, while viscoelasticity operates via mechanotransduction pathways. Additionally, our investigation revealed a synergistic effect between LC state and viscoelasticity, amplifying cell-protein interactions and osteogenic mechanotransduction processes. Furthermore, the interesting mechanochromic response observed in the LC hydrogel scaffolds suggests their potential application in mechanosensing. Our findings shed light on the mechanisms and synergistic effects of LC state and viscoelasticity in osteoid on osteogenesis, offering valuable insights for the biomimetic design of bone repair scaffolds.

In order to achieve better starting performance of diesel engine in extreme low-temperature environment, the relevant parameters affecting the starting of diesel engine were researched. Through orthogonal simulation, the influence of environmental factors (intake pressure, intake temperature), design parameters (compression ratio, combustor reentrant ratio, nozzle diameter), control parameters (injection temperature, pilot injection quantity, start of main injection, main injection duration, injection interval between pilot injection and main injection) on diesel engine starting process under low-temperature conditions were studied. The key parameters affecting the starting process of diesel engine were extracted by range analysis. Meanwhile the parameters matching of each factor were studied by taking the cylinder pressure, the cylinder temperature and the instantaneous heat release rate as evaluation indexes. The results show that the environmental factors and control parameters have a higher degree of influence on the starting process of diesel engine. Intake pressure, intake temperature, start of main injection and main injection duration are the key parameters affecting the starting of diesel engine under low temperature conditions, and combination one is selected as the best parameter matching combination. The key parameters influencing the low temperature starting process of diesel engine are obtained, which provides a theoretical basis for improving the starting effect of diesel engine under low temperature.

Aimed at low-cycle fatigue damage of Z2CND18.12N austenitic stainless steel for nuclear power pipelines，the influences of the acquisition and post-processing parameters on the local misorientation （ML） were studied by electron backscattered diffraction （EBSD） technique. The damage evolution of grains with typical orientations was discussed based on the parameters after optimization. The results show that the step size，filter and binning all affect the value of ML. Taking into account factors such as grain size，testing accuracy， and efficiency，the optimal selection is to determine binning 2×2， filter 11×11， and testing step size of 2 μm or 5 μm，respectively. Two damage regions with different levels are characterized. The peak and average values of ΔML in 〈111〉 orientation are higher than those in 〈101〉 and 〈001〉 orientations，and the values of ΔML in 〈101〉 orientation are the smallest. Large ML is observed in small grains，especially in the grain boundaries and intersections. Meanwhile，non-uniformity of deformation distribution was discussed in according to the effects of grain size and grain boundary. It is confirmed that ML can effectively evaluate the deformation damage of Z2CND18.12N steel，which is valuable for the development of material and structural damage evaluation technology based on multi-physical parameters.

Abstract The second-order nonlinear Hall effect (NLHE) in non-centrosymmetric materials has recently drawn intense interest, since its inherent rectification could enable various device applications such as energy harvesting and wireless charging. However, previously reported NLHE systems normally suffer from relatively small Hall voltage outputs and/or low working temperatures. In this study, we report the observation of a pronounced NLHE in tellurium (Te) thin flakes at room temperature. Benefiting from the semiconductor nature of Te, the obtained nonlinear response can be readily enhanced through electrostatic gating, leading to a second-harmonic output at 300 K up to 2.8 mV. By utilizing such a giant NLHE, we further demonstrate the potential of Te as a wireless Hall rectifier within the radiofrequency range, which is manifested by the remarkable and tunable rectification effect also at room temperature. Extrinsic scattering is then revealed to be the dominant mechanism for the NLHE in Te, with symmetry breaking on the surface playing a key role. As a simple elemental semiconductor, Te provides an appealing platform to advance our understanding of nonlinear transport in solids and to develop NLHE-based electronic devices.

Abstract Objective Incontinence seriously affects the lives of middle‐aged and older people. Pelvic floor muscle assessment is very important for incontinence, and handgrip strength can be used as an auxiliary diagnostic tool. Our study aims to find new cutoff points of handgrip strength as early indicators of incontinence and analyze the association between low handgrip strength and incontinence among Chinese middle‐aged and older people. Methods Participants were recruited from the 2015 China Health and Retirement Longevity Study. Receiver operating characteristic (ROC) curves were used to find the handgrip strength cutoff point. Logistic regression analysis was performed to explore other incontinence‐related risk factors. Results The study included 10,229 middle‐aged and older people. Compared with normal handgrip strength participants, medium strength participants had 1.510 [men, 95% confidence interval (CI) = 1.017–2.243] and 1.792 (women, 95% CI = 1.294–2.480) times greater risk of incontinence, and low strength participants had 2.420 (men, 95% CI = 1.787–3.277) and 1.516 (women, 95% CI = 1.130–2.032) times greater risk of incontinence. Trend test results showed that the risk of incontinence increased with decreasing handgrip strength in middle‐aged and older people. Conclusions Our study suggests that handgrip strength

Abstract The whole-cell inorganic-biohybrid systems show special functions and wide potential in biomedical application owing to the exceptional interactions between microbes and inorganic materials. However, the hybrid systems are still in stage of proof of concept. Here, we report a whole-cell inorganic-biohybrid system composed of Spirulina platensis and gold nanoclusters (SP-Au), which can enhance the cancer radiotherapy through multiple pathways, including cascade photocatalysis. Such systems can first produce oxygen under light irradiation, then convert some of the oxygen to superoxide anion (•O2 −), and further oxidize the glutathione (GSH) in tumor cells. With the combination of hypoxic regulation, •O2 − production, GSH oxidation, and the radiotherapy sensitization of gold nanoclusters, the final radiation is effectively enhanced, which show the best antitumor efficacy than other groups in both 4T1 and A549 tumor models. Moreover, in vivo distribution experiments show that the SP-Au can accumulate in the tumor and be rapidly metabolized through biodegradation, further indicating its application potential as a new multiway enhanced radiotherapy sensitizer.

The evolutionary dynamics of cancer, characterized by its profound heterogeneity, demand sophisticated tools for a holistic understanding. This review delves into tumor phylogenetics, an essential approach bridging evolutionary biology with oncology, offering unparalleled insights into cancer's evolutionary trajectory. We provide an overview of the workflow, encompassing study design, data acquisition, and phylogeny reconstruction. Notably, the integration of diverse data sets emerges as a transformative step, enhancing the depth and breadth of evolutionary insights. With this integrated perspective, tumor phylogenetics stands poised to redefine our understanding of cancer evolution and influence therapeutic strategies.

Abstract To define the characteristics of fundus manifestations in patients after SARS-CoV-2 infection with multimodal imaging techniques. This is a retrospective multicenter and multimodal imaging study including 90 patients. All patients with a visual complaint occurring immediately after SARS-CoV-2 infection were referred to six clinics between December 2022 and February 2023. Demographic information and the temporal relationship between SARS-CoV-2 infection and visual symptoms were documented. The characteristics of the fundus lesions were evaluated using multimodal imaging. Ninety patients from six hospitals were included in this study, including 24 males (26.67%) and 66 (73.33%) females. Seventy-eight patients (86.66%) (146 eyes) were diagnosed with Acute Macular Neuroretinopathy (AMN). The AMN patients were primarily young women (67.95%). Sixty-eight patients (87.18%) had AMN in both eyes. Thirty-eight eyes (24.36%) included Purtscher or Purtscher-like lesions. optical coherence tomography and infrared retinal photographs can show AMN lesions well. Eleven cases were diagnosed with simple Purtscher or Purtscher-like retinopathy (2 cases, 2.22%), Vogt‒Koyanagi‒Harada (VKH) syndrome or VKH-like uveitis (3 cases, 3.33%), multiple evanescent white-dot syndrome (MEWDS) (2 cases, 2.22%), and rhino-orbital-cerebral mucormycosis (ROCM) (5 cases, 5.56%). After SARS-CoV-2 infection, diversified fundus lesions were evident in patients with visual complaints. In this report, AMN was the dominant manifestation, followed by Purtscher or Purtscher-like retinopathy, MEWDS, VKH-like uveitis, and ROCM.