An ultra-long-acting L-asparaginase synergizes with an immune checkpoint inhibitor in starvation-immunotherapy of metastatic solid tumors.

Metastasis stands as the primary contributor to mortality associated with tumors. Chemotherapy and immunotherapy are frequently utilized in the management of metastatic solid tumors. Nevertheless, these therapeutic modalities are linked to serious adverse effects and limited effectiveness in preventing metastasis. Here, we report a novel therapeutic strategy named starvation-immunotherapy, wherein an immune checkpoint inhibitor is combined with an ultra-long-acting L-asparaginase that is a fusion protein comprising L-asparaginase (ASNase) and an elastin-like polypeptide (ELP), termed ASNase-ELP. ASNase-ELP's thermosensitivity enables it to generate an in-situ depot following an intratumoral injection, yielding increased dose tolerance, improved pharmacokinetics, sustained release, optimized biodistribution, and augmented tumor retention compared to free ASNase. As a result, in murine models of oral cancer, melanoma, and cervical cancer, the antitumor efficacy of ASNase-ELP by selectively and sustainably depleting L-asparagine essential for tumor cell survival was substantially superior to that of ASNase or Cisplatin, a first-line anti-solid tumor medicine, without any observable adverse effects. Furthermore, the combination of ASNase-ELP and an immune checkpoint inhibitor was more effective than either therapy alone in impeding melanoma metastasis. Overall, the synergistic strategy of starvation-immunotherapy holds excellent promise in reshaping the therapeutic landscape of refractory metastatic tumors and offering a new alternative for next-generation oncology treatments.

Significant spatiotemporal pattern of nitrous oxide emission and its influencing factors from a shallow eutropic lake in Inner Mongolia, China.

Eutrophic shallow lakes are generally considered as a contributor to the emission of nitrous oxide (N2O), while regional and global estimates have remained imprecise. This due to a lack of data and insufficient understanding of the multiple contributing factors. This study characterized the spatiotemporal variability in N2O concentrations and N2O diffusive fluxes and the contributing factors in Lake Wuliangsuhai, a typical shallow eutrophic and seasonally frozen lake in Inner Mongolia with cold and arid climate. Dissolved N2O concentrations of the lake exhibited a range of 4.5 to 101.2 nmol/L, displaying significant spatiotemporal variations. The lowest and highest concentrations were measured in summer and winter, respectively. The spatial distribution of N2O flux was consistent with that of N2O concentrations. Additionally, the hotspots of N2O emissions were detected within close to the main inflow of lake. The wide spatial and temporal variation in N2O emissions indicate the complexity and its relative importance of factors influencing emissions. N2O emissions in different lake zones and seasons were regulated by diverse factors. Factors influencing the spatial and temporal distribution of N2O concentrations and fluxes were identified as WT, WD, DO, Chl-a, SD and COD. Interestingly, the same factor demonstrated opposing effects on N2O emission in various seasons or zones. This research improves our understanding of N2O emissions in shallow eutrophic lakes in cold and arid areas.

Fiber Microstructure Quantile (FMQ) Regression: A Novel Statistical Approach for Analyzing White Matter Bundles from Periphery to Core.

The structural connections of the brain's white matter are critical for brain function. Diffusion MRI tractography enables the in-vivo reconstruction of white matter fiber bundles and the study of their relationship to covariates of interest, such as neurobehavioral or clinical factors. In this work, we introduce Fiber Microstructure Quantile (FMQ) Regression, a new statistical approach for studying the association between white matter fiber bundles and scalar factors (e.g., cognitive scores). Our approach analyzes tissue microstructure measures based on quantile-specific bundle regions . These regions are defined according to the quantiles of fractional anisotropy (FA) from the periphery to the core of a population fiber bundle, which pools all individuals' bundles. To investigate how fiber bundle tissue microstructure relates to covariates of interest, we employ the statistical technique of quantile regression. Unlike ordinary regression, which only models a conditional mean, quantile regression models the conditional quantiles of a response variable. This enables the proposed analysis, where a quantile regression is fitted for each quantile-specific bundle region. To demonstrate FMQ Regression, we perform an illustrative study in a large healthy young adult tractography dataset derived from the Human Connectome Project-Young Adult (HCP-YA), focusing on particular bundles expected to relate to particular aspects of cognition and motor function. Importantly, our analysis considers sex-specific effects in brain-behavior associations. In comparison with a traditional method, Automated Fiber Quantification (AFQ), which enables FA analysis in regions defined along the trajectory of a bundle, our results suggest that FMQ Regression is much more powerful for detecting brain-behavior associations. Importantly, FMQ Regression finds significant brain-behavior associations in multiple bundles, including findings unique to males or to females. In both males and females, language performance is significantly associated with FA in the left arcuate fasciculus, with stronger associations in the bundle's periphery. In males only, memory performance is significantly associated with FA in the left uncinate fasciculus, particularly in intermediate regions of the bundle. In females only, motor performance is significantly associated with FA in the left and right corticospinal tracts, with a slightly lower relationship at the bundle periphery and a slightly higher relationship toward the bundle core. No significant relationships are found between executive function and cingulum bundle FA. Our study demonstrates that FMQ Regression is a powerful statistical approach that can provide insight into associations from bundle periphery to bundle core. Our results also identify several brain-behavior relationships unique to males or to females, highlighting the importance of considering sex differences in future research.

A Self-Immobilizing Photosensitizer with Long-Term Retention for Hypoxia Imaging and Enhanced Photodynamic Therapy.

The precise theranostic strategy of fluorescence imaging-guided photodynamic therapy (PDT) can effectively mitigate the adverse effect of photosensitizers in normal cells and tissues. However, low tumor enrichment and high diffusivity of photosensitizers significantly compromise the imaging accuracy and PDT effect. In this study, we have developed a nitroreductase (NTR)-activated and self-immobilizing photosensitizer CyNT-F, which showed enhanced enrichment in tumor tissues and facilitated precise and sustained imaging as well as PDT for hypoxia tumors. mPEG-b-PDPA nanomicelles encapsulating photosensitizers underwent dissociation and released CyNT-F in tumor cells. CyNT-F and NTR enzymatically reacted in situ to generate highly reactive quinone methide, subsequently covalently binding to adjacent proteins for fluorescence and PDT activation. CyNT-F exhibited longer intracellular retention (7 days) and effectively inhibited the tumor growth of solid hypoxia tumor. We believe the activatable and self-immobilizing strategy of PDT presents a novel methodology for minimizing the adverse effect and enabling spatiotemporally accurate ablation of diseased cells and tissues.

Plumbagin, a novel TRPV2 inhibitor, ameliorates microglia activation and brain injury in a middle cerebral artery occlusion/reperfusion mouse model.

BACKGROUND AND PURPOSE: Transient receptor potential vanilloid 2 (TRPV2) is a Ca2+-permeable non-selective cation channel. Despite the significant roles of TRPV2 in immunological response, cancer progression and cardiac development, pharmacological probes of TRPV2 remain to be identified. We aimed to discover TRPV2 inhibitors and to elucidate their molecular mechanism of action. EXPERIMENTAL APPROACH: Fluorescence-based Ca2+ assay in HEK-293 cells expressing murine TRPV2 was used to identify plumbagin as a novel TRPV2 inhibitor. Patch-clamp, in silico docking and site-directed mutagenesis were applied to investigate the molecular mechanisms critical for plumbagin interaction. ELISA and qPCR were used to assess nitric oxide release and mRNA levels of inflammatory mediators, respectively. si-RNA interference was used to knock down TRPV2 expression, which was validated by western blotting. Neurological and histological analyses were used to examine brain injury of mice following middle cerebral artery occlusion/reperfusion (MCAO/R). KEY RESULTS: Plumbagin is a potent TRPV2 negative allosteric modulator with an IC50 value of 0.85 µM, exhibiting >14-fold selectivity over TRPV1, TRPV3 and TRPV4. Plumbagin suppresses TRPV2 activity by decreasing the channel open probability without affecting the unitary conductance. Moreover, plumbagin binds to an extracellular pocket formed by the pore helix and flexible loop between transmembrane helices S5 and S6 of TRPV2. Plumbagin effectively suppresses LPS-induced inflammation of BV-2 microglia and ameliorates brain injury of MCAO/R mice. CONCLUSION AND IMPLICATIONS: Plumbagin is a novel pharmacological probe to study TRPV2 pathophysiology. TRPV2 is a novel molecular target for the treatment of neuroinflammation and ischemic stroke.

Therapeutic effects of Kangxian Yanshen formula on patients with chronic kidney disease stages 3-4: a retrospective cohort study.

Background: This study retrospectively evaluated the actual efficacy of Kangxian Yanshen Formula Chinese medicine on renal function-related indicators in chronic kidney disease (CKD) stage 3-4 patients. Methods: In this retrospective cohort study, we collected 212 adult CKD patients with baseline estimated glomerular filtration rate (eGFR) of 15-60 ml/min/1.73 m2. All participants received usual care (i.e., Western medications), and participants in the exposure group (n = 109) were additionally prescribed Kangxian Yanshen Formula Chinese medicine. The primary outcome was an adjusted hazard risk and 95% confidence interval (95% CI) of a 30% decrease in eGFR at month 36 from baseline. Results: In terms of eGFR, among participants treated with additional Kangxian Yanshen Formula, after adjusting for covariates, there was a 57.1% reduction in the risk of a 30% decline from baseline in eGFR among participants in the Kangxian Yanshen Formula group compared with the Western medicine group (adjusted hazard risk: 0.429; 95% CI 0.269-0.682). In addition, participants in the Kangxian Yanshen Formula group had a significantly higher change in eGFR from baseline to month 12 than those in the western medicine group (3.40 ± 11.62 versus -3.87 ± 8.39; between-group difference Δ5.61 [± 2.26 standard deviation] mL/min/1.73 m2; P = 0.014). Participants in both groups showed a decreasing trend in eGFR at months 24 and 36. Conclusion: In patients with stage 3-4 CKD, Kangxian Yanshen Formula Chinese medicine therapy may help delay eGFR decline, but high-quality randomized controlled trials are needed to validate the results further.

Advancing infrared and visible image fusion with an enhanced multiscale encoder and attention-based networks.

Infrared and visible image fusion aims to produce images that highlight key targets and offer distinct textures, by merging the thermal radiation infrared images with the detailed texture visible images. Traditional auto encoder-decoder-based fusion methods often rely on manually designed fusion strategies, which lack flexibility across different scenarios. Addressing this limitation, we introduce EMAFusion, a fusion approach featuring an enhanced multiscale encoder and a learnable, lightweight fusion network. Our method incorporates skip connections, the convolutional block attention module (CBAM), and nest architecture within the auto encoder-decoder framework to adeptly extract and preserve multiscale features for fusion tasks. Furthermore, a fusion network driven by spatial and channel attention mechanisms is proposed, designed to precisely capture and integrate essential features from both image types. Comprehensive evaluations of the TNO image fusion dataset affirm the proposed method's superiority over existing state-of-the-art techniques, demonstrating its potential for advancing infrared and visible image fusion.

Melatonin protects against sarcopenia in middle-aged mice.

BACKGROUND: Sarcopenia is a common age-related disease. Melatonin (MEL) is an age-related endocrine hormone, which displays a crucial role in resisting oxidative stress during aging. Importantly, the antioxidant properties of MEL can be mediated by mitochondria. OBJECTIVE: Therefore, we wondered whether MEL could mitigate oxidative stress caused by mitochondria in sarcopenia. METHODS: The middle-aged mice were administered 5 mg/kg/d and 10 mg/kg/d of MEL for 2 months. Young mice were used as the control group. RESULTS: After treatment with MEL, the grip strength of the fore/hind limbs, running time, and distance were elevated, and the weights of the gastrocnemius (GA), tibialis anterior (TA), extensor digitorum longus (EDL), and soleus (SOL) were enhanced in middle-aged mice. Additionally, MEL was observed to alleviate histological damage and increase the cross-sectional area of muscle fibers in GA tissues of middle-aged mice. Furthermore, following MEL treatment, there was an increase in the percentage and size of normal mitochondria as well as mtDNA copy number but a reduction in the levels of malondialdehyde (MDA), protein carbonyl, and reactive oxygen species (ROS) in the GA tissues of middle-aged mice. At the molecular level, MEL repressed the levels of ATROGIN-1, muscle RING-finger protein-1 (MURF-1), and the ratio of p-P38/P38, but elevated the expression of cytochrome c oxidase subunit 4 (COX4), cystatin C (CYTC), nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in the GA tissues of middle-aged mice. Importantly, 10 mg/kg MEL was more efficacious in the treatment of sarcopenia than 5 mg/kg MEL. CONCLUSION: MEL attenuates sarcopenia in middle-aged mice, and the mechanism may relate to mitochondria-induced oxidative stress and the PGC-1α/TFAM pathway.

NIR-II Anti-Stokes Luminescence Nanocrystals with 1710 nm Excitation for in vivo Bioimaging.

Anti-Stokes luminescence (ASL) based on lanthanide nanocrystals holds immense promise for in vivo optical imaging and bio-detection, which benefits from filtered autofluorescence. However, the current longest emission and excitation wavelengths of lanthanide ASL system were shorter than 1200 nm and 1532 nm, respectively, which limited tissue penetration depth and caused low signal-to-noise ratio (SNR) of in vivo imaging due to tissue scattering and water absorption. In this work, we extended the excitation wavelength to 1710 nm with the second near-infrared (NIR-II, 1000-1700 nm) emission up to 1650 nm through a novel ASL nanocrystal LiYF4:10%Tm@LiYF4:70%Er@LiYF4. Compared with 1532 nm excited ASL nanoprobes, the 1710 nm excited nanocrystals could improve in vivo imaging SNR by 12.72 folds. Based on this excellent imaging performance of the proposed ASL nanoprobes, three-channel in vivo dynamic multiplexed imaging was achieved, which quantitatively revealed metabolic rates of intestinal dynamics and liver enrichment under anesthetized and awake states. This innovative ASL nanoprobes and dynamic multiplexed imaging technology would be conducive to optimizing dosing regimen and treatment plans across various physiological conditions.

A Programme of Hepatitis C Surveillance With Active Linkage to Care (HEAL) for Inpatients in Two Tertiary Hospitals in Jiangsu, China.

Hepatitis C virus (HCV) infection is a major public health burden in China, affecting more than 10 million individuals. We aimed to evaluate the effectiveness of a hospital-based intervention programme for HCV Surveillance with linkage to care (HEAL) in a prospective cohort. The HEAL programme was carried out targeting inpatients from non-infectious departments of two tertiary hospitals in Jiangsu, China. It consisted of an educational campaign to raise awareness of physicians from non-IDs to promote HCV surveillance, a patient-navigator-centred clinical algorithm responsible for the efficient follow-up of patients with positive HCV antibody, including comprehensive testing, diagnosis and treatment. We characterised the rate of linkage to HCV diagnosis, care and treatment during the pre-intervention period (from 1 July 2016 and June 30, 2018) and after the intervention (from March 2019 to May 2021). During the pre-intervention period, 89,303 (45.3%) out of 196,780 non-ID inpatients were screened for anti-HCV, and 631 patients were tested positive. One hundred and fifty-six (24.7%) patients was followed up for HCV RNA confirmatory testing, and 58 (37.1%) of patients further were diagnosed with chronic HCV infection (CHC). Only 18 (31.3%) of the diagnosed patients with CHC were linked to hepatitis C clinics for treatment, 10 (55.6%) patients received antiviral regimen. Among them, two (11.1%) received DAA treatment, while eight (44.4%) adopted peginterferon/ribavirin regimen. During the intervention period, 232,275 patients were hospitalised in non-infectious department and 151,203 (65.1%) were screened for anti-HCV. Of these, 960 patients tested positive for HCV antibodies, resulting in a prevalence of anti-HCV positivity of 0.63%. Six hundred and seventy (69.8%) patients were enrolled, and 100% were followed up for HCV RNA confirmatory testing. Two hundred and ninety-one (43.4%) individuals with active HCV were identified. Two hundred and thirty-eight (81.8%) of HCV-infected individuals were linked to HCV care, and 157 (65.9%) were linked to treatment. Compared to the pre-intervention period, there was a 2.61-fold increase in the percentage of patients linked to care and a 5.94-fold increase in the proportion of patients who started DAAs therapy. This HEAL programme achieved enhanced HCV Surveillance with linkage to care, which has been demonstrated as an effective strategy in the hospital setting to improve the hepatitis C care continuum by identifying inpatients unaware of their HCV status and facilitating their access to HCV treatment.

Key targets of signal transduction neural mechanisms in acupuncture treatment of cardiovascular diseases: Hypothalamus and autonomic nervous system.

Background: Cardiovascular disease is the leading cause of death worldwide. As a traditional Chinese treatment method, acupuncture has a unique role in restoring the balance of the human body environment. Due to its safety, non-invasive nature, and effectiveness in treating cardiovascular diseases, acupuncture has been widely welcomed and recognized among the world. A large amount of evidence shows that acupuncture can effectively regulate cardiovascular diseases through the autonomic nervous system. The hypothalamus, as an important component of regulating the autonomic nervous system, plays an important role in regulating the internal environment, maintaining homeostasis, and preserving physiological balance. However, there is currently a scarcity of review articles on acupuncture signal transduction and acupuncture improving cardiovascular disease through the hypothalamus and autonomic nervous system. Objective: This review delves into the transduction of acupuncture signals and their neural regulatory mechanisms on the hypothalamus and autonomic nervous system, elucidating their impact on cardiovascular disease. Methods: Review the basic and clinical studies on acupuncture signal transduction mechanisms and the role of the hypothalamus and ANS in acupuncture treatment of cardiovascular diseases published in four English databases (PubMed, Web of Science, MEDLINE, and Springer Cochrane Library) and two Chinese databases (Wanfang Database and China National Knowledge Infrastructure Database) over the past 20 years. Results: Through sensory stimulation, acupuncture effectively transmits signals from the periphery to the hypothalamus, where they are integrated, and finally regulate the autonomic nervous system to treat cardiovascular diseases. Discussion: Acupuncture exhibits significant potential as a therapeutic modality for cardiovascular diseases by orchestrating autonomic nervous system regulation via the hypothalamus, thereby gifting novel perspectives and methodologies for the prevention and treatment of cardiovascular ailments.

Comparison of resting-state brain activity between insomnia and generalized anxiety disorder: A coordinate-based meta-analysis.

Patients with insomnia disorder (ID) usually experience a greater burden of comorbid anxiety symptoms. However, the neural mechanism under the mutual relationship between ID and anxiety remains largely unclear. The meta-analysis aimed to explore the concordance and distinction of regional brain functional activity in patients with ID and those with generalized anxiety disorder (GAD) using coordinate-based activation likelihood estimation approach. Studies using resting-state regional homogeneity, amplitude of low-frequency fluctuations (ALFF), or fractional ALFF in patients with ID or GAD were included by searching multiple databases up to May 24, 2024. Using meta-analytic approach, 21 studies of ID vs. healthy controls (HC) and 16 studies of GAD vs. HC were included to illuminate the common and distinct patterns between the two disorders. Results showed that ID and GAD shared increased brain activities in the left posterior cingulate cortex and left precuneus, as well as decreased brain activity in the left medial prefrontal cortex. Additionally, compared with ID, GAD showed greater increased activities in the left superior frontal gyrus. Our study reveals both common and different activation patterns between ID and GAD, which may provide novel insights for understanding the neural basis of the two disorders and enlighten the possibility of the development of more targeted treatment strategies for ID and GAD.

Neuromodulation in Spinal Cord Injury Using Transcutaneous Spinal Stimulation-Mapping for a Blood Pressure Response: A Case Series.

Spinal cord transcutaneous stimulation (scTS) offers a promising approach to enhance cardiovascular regulation in individuals with a high-level spinal cord injury (SCI), addressing the challenges of unstable blood pressure (BP) and the accompanying hypo- and hypertensive events. While scTS offers flexibility in stimulation locations, it also leads to significant variability and lack of validation in stimulation sites utilized by studies. Our study presents findings from a case series involving eight individuals with chronic cervical SCI, examining the hemodynamic effects of scTS applied in different vertebral locations, spanning from high cervical to sacral regions. Stimulation of the lumbosacral vertebrae region (L1/2, S1/2, and also including T11/12) significantly elevated BP, unlike cervical or upper thoracic stimulation. The observed trend, which remained consistent across different participants, highlights the promising role of lumbosacral stimulation in neuromodulating BP.

Assessment of the Depiction of Superficial White Matter Using Ultra-High-Resolution Diffusion MRI.

The superficial white matter (SWM) consists of numerous short-range association fibers connecting adjacent and nearby gyri and plays an important role in brain function, development, aging, and various neurological disorders. Diffusion MRI (dMRI) tractography is an advanced imaging technique that enables in vivo mapping of the SWM. However, detailed imaging of the small, highly-curved fibers of the SWM is a challenge for current clinical and research dMRI acquisitions. This work investigates the efficacy of mapping the SWM using in vivo ultra-high-resolution dMRI data. We compare the SWM mapping performance from two dMRI acquisitions: a high-resolution 0.76-mm isotropic acquisition using the generalized slice-dithered enhanced resolution (gSlider) protocol and a lower resolution 1.25-mm isotropic acquisition obtained from the Human Connectome Project Young Adult (HCP-YA) database. Our results demonstrate significant differences in the cortico-cortical anatomical connectivity that is depicted by these two acquisitions. We perform a detailed assessment of the anatomical plausibility of these results with respect to the nonhuman primate (macaque) tract-tracing literature. We find that the high-resolution gSlider dataset is more successful at depicting a large number of true positive anatomical connections in the SWM. An additional cortical coverage analysis demonstrates significantly higher cortical coverage in the gSlider dataset for SWM streamlines under 40 mm in length. Overall, we conclude that the spatial resolution of the dMRI data is one important factor that can significantly affect the mapping of SWM. Considering the relatively long acquisition time, the application of dMRI tractography for SWM mapping in future work should consider the balance of data acquisition efforts and the efficacy of SWM depiction.

Recent advances and current status of gene therapy for epilepsy.

BACKGROUND: Epilepsy is a common neurological disorder with complex pathogenic mechanisms, and refractory epilepsy often lacks effective treatments. Gene therapy is a promising therapeutic option, with various preclinical experiments achieving positive results, some of which have progressed to clinical studies. DATA SOURCES: This narrative review was conducted by searching for papers published in PubMed/MEDLINE with the following single and/or combination keywords: epilepsy, children, neurodevelopmental disorders, genetics, gene therapy, vectors, transgenes, receptors, ion channels, micro RNAs (miRNAs), clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)9 (CRISPR/Cas9), expression regulation, optogenetics, chemical genetics, mitochondrial epilepsy, challenges, ethics, and disease models. RESULTS: Currently, gene therapy research in epilepsy primarily focuses on symptoms attenuation mediated by viral vectors such as adeno-associated virus and other types. Advances in gene therapy technologies, such as CRISPR/Cas9, have provided a new direction for epilepsy treatment. However, the clinical application still faces several challenges, including issues related to vectors, models, expression controllability, and ethical considerations. CONCLUSIONS: Here, we summarize the relevant research and clinical advances in gene therapy for epilepsy and outline the challenges facing its clinical application. In addition to the shortcomings inherent in gene therapy components, the reconfiguration of excitatory and inhibitory properties in epilepsy treatment is a delicate process. On-demand, cell-autonomous treatments and multidisciplinary collaborations may be crucial in addressing these issues. Understanding gene therapy for epilepsy will help clinicians gain a clearer perception of the research progress and challenges, guiding the design of future clinical protocols and research decisions.

Impacts of compatibility between rainwater availability and water demand on water saving performance of rainwater harvesting systems.

Rainwater Harvesting Systems (RHS) are widely implemented to mitigate urban water shortages, yet the impacts of compatibility between rainwater availability and water demand on their performance are often overlooked. This study introduces novel rainwater deficit and surplus indices to quantitatively assess the impacts of compatibility between rainwater availability and water demand on the performance of RHS across 16 cities in different climate zones and under 3 daily water demand scenarios. The rainwater deficit and surplus indices, and the water saving efficiency and reliability of RHS are calculated based on long-term (1991-2020) continuous simulations using a daily water balance model. Results show the rainwater deficit index effectively quantifies water supply pressure on RHS, while the rainwater surplus index quantitatively evaluates their water saving potential. Both of water saving efficiency and reliability of RHS significantly linearly decrease with the rainwater deficit index (P < 0.05), and the coefficients of determination (R2) decrease from 0.96 to 0.80 as tank size increases from 1 to 300 m3. Both of water saving efficiency and reliability increase along sigmoid curves with the rainwater surplus index (P < 0.05), and R2 values increase from 0.91 to 0.99 with tank size. The results indicate that tank size optimization enhances water saving performance of RHS through reducing deficits and surpluses. However, the performance enhancement by tank size optimization could be limited by the compatibility between rainwater availability and water demand. Taken Kashgar (arid climate) as an example, the thresholds of water saving efficiency under all water demand scenarios are below 15% due to high rainwater deficit and low surplus. This study emphasizes that the compatibility between rainwater availability and water demand should be considered in planning and design of RHS.

T2T genome assemblies of Fallopia multiflora (Heshouwu) and F. multiflora var. angulata.

The traditional Chinese medicinal plant Fallopia multiflora (hereafter AYY) is well known for its anti-hyperlipidaemia, immunomodulating, and hepatoprotective effects, attributed to its abundance of anthraquinones and stilbene glycosides, which are distinct to its variety F. multiflora var. angulata (hereafter CYY) in proportion and composition. In this study, telomere-to-telomere (T2T) genomes were assembled for AYY and CYY using PacBio HiFi reads and Hi-C data. The genome sizes, percentages of repetitive sequences, and numbers of protein-coding genes of AYY and CYY assemblies were 1,458.37 Mb/70.48%/84,768 and 1,174.38 Mb/67.36%/69,100, respectively. Comprehensive assessments confirmed high continuity (contig N50: 112.58 Mb and 94.83 Mb; number of gaps: 9 and 5), completeness (BUSCOs: 97.30% and 97.60%; LAI: 16.93 and 16.77), and correctness (QV: 51.42 and 52.60) of AYY and CYY assemblies. These T2T genomes of F. multiflora provide valuable resources for studying the biosynthesis of specialized metabolites and facilitating precise genetic improvement.

Analysis on the related factors of misplacement of freehand pedicle screws via posterior approach in degenerative scoliosis.

BACKGROUND: To study the risk factors associated with misplacement of freehand pedicle screws through a posterior approach for degenerative scoliosis. METHODS: A total of 204 patients who underwent posterior pedicle screw-rod system surgery for degenerative scoliosis in our hospital from December 2020 to December 2023 were retrospectively analyzed. Patient demographics, radiographic accuracy, and surgery-related information were recorded. RESULTS: A total of 204 patients were included. A total of 2496 screws were placed. 2373 (95.07%) were in good position. Misplacement screws were 123 (4.93%). None of the patients had postoperative spinal nerve symptoms due to screw malposition. The misplacement rate of thoracic (T10-T12) pedicle screws was 11.11% (60/540). Misplacement of pedicle screws in the lumbar spine (L1-L5) was 3.22% (63/1956). Age, gender, surgeon, and operation time had no significant effect on misplacement of pedicle screws (P>0.05). Body mass index, Hu value, number of screw segments, Cobb angle, vertebral rotation, and spinal canal morphology had some correlation with pedicle screw misplacement. Among them, BMI, Hu value, number of screw segments, Cobb angle, and vertebral rotation grade were independent risk factors for PS misplacement (P<0.05). The height of the posterior superior iliac spine had a significant effect on pedicle screw misplacement in the lower lumbar spine (L4/5) (P<0.05). CONCLUSION: BMI, Hu value, number of screw levels, Cobb angle, and vertebral rotation grade were independent risk factors for pedicle screw misplacement in patients with degenerative scoliosis. Posterior superior iliac spine height has a large impact on PS placement in the lower lumbar spine. Patients with degenerative scoliosis should be preoperatively planned for the size and direction of the placed screws by X-ray and CT three-dimensional, to reduce the misplacement rate of pedicle screws.

Federated Cross-Incremental Self-Supervised Learning for Medical Image Segmentation.

Federated cross learning has shown impressive performance in medical image segmentation. However, it encounters the catastrophic forgetting issue caused by data heterogeneity across different clients and is particularly pronounced when simultaneously facing pixelwise label deficiency problem. In this article, we propose a novel federated cross-incremental self-supervised learning method, coined FedCSL, which not only can enable any client in the federation incrementally yet effectively learn from others without inducing knowledge forgetting or requiring massive labeled samples, but also preserve maximum data privacy. Specifically, to overcome the catastrophic forgetting issue, a novel cross-incremental collaborative distillation (CCD) mechanism is proposed, which distills explicit knowledge learned from previous clients to subsequent clients based on secure multiparty computation (MPC). Besides, an effective retrospect mechanism is designed to rearrange the training sequence of clients per round, further releasing the power of CCD by enforcing interclient knowledge propagation. In addition, to alleviate the need of large-scale densely annotated pretraining medical datasets, we also propose a two-stage training framework, in which federated cross-incremental self-supervised pretraining paradigm first extracts robust yet general image-level patterns across multi-institutional data silos via a novel round-robin distributed masked image modeling (MIM) pipeline; then, the resulting visual concepts, e.g., semantics, are transferred to the federated cross-incremental supervised fine-tuning paradigm, favoring various cross-silo medical image segmentation tasks. The experimental results on public datasets demonstrate the effectiveness of the proposed method as well as the consistently superior performance of our method over most state-of-the-art methods quantitatively and qualitatively.

Vinylene-Linking of Polycyclic Aromatic Hydrocarbons to π-Extended Two-Dimensional Covalent Organic Framework Photocatalyst for H2O2 Synthesis.

Polycyclic aromatic hydrocarbons (PAHs) hold the predominant role either as individual molecules or building blocks in the field of organic semiconductors or nanocarbons. Connecting PAHs via sp2-carbon bridges to form high-crystalline p-extended structures is highly desired not only for enlarging the regimes of two-dimensional materials but also for achieving exceptional properties/functions. In this work, we developed 5,10-dimethyl-4,9-diazapyrene as a key monomer, whose two methyl groups at the positions adjacent to nitrogen atoms, can helpfully increase the solubility, and serve as the active connection sites. In the presence of organic acids, this monomer enables smoothly conducting Knoevenagel condensation to form two vinylene-linked PAH-cored COFs, which show high-crystalline honeycomb structures with large surface areas up to 1238 m2 g-1. Owing to the direct connection mode of PAH building blocks with vinylene, the as-prepared COFs possess spatially extended p-conjugation and substantial semiconducting properties. Consequently, their visible-light photocatalysis with exceptional activity and durability was manifested to generate H2O2 up to 3820 µmol g-1 h-1 in pure water, and even 17080 µmol g-1 h-1 using benzyl alcohol as a hole sacrificial agent.