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Abstract Maladaptive changes of metabolic patterns in the lumbar dorsal root ganglion (DRG) are critical for nociceptive hypersensitivity genesis. The accumulation of branched-chain amino acids (BCAAs) in DRG has been implicated in mechanical allodynia and thermal hyperalgesia, but the exact mechanism is not fully understood. This study aimed to explore how BCAA catabolism in DRG modulates pain sensitization. Wildtype male mice were fed a high-fat diet (HFD) for 8 weeks. Adult PP2Cmfl/fl mice of both sexes were intrathecally injected with pAAV9-hSyn-Cre to delete the mitochondrial targeted 2 C-type serine/threonine protein phosphatase (PP2Cm) in DRG neurons. Here, we reported that BCAA catabolism was impaired in the lumbar 4–5 (L4-L5) DRGs of mice fed a high-fat diet (HFD). Conditional deletion of PP2Cm in DRG neurons led to mechanical allodynia, heat and cold hyperalgesia. Mechanistically, the genetic knockout of PP2Cm resulted in the upregulation of C-C chemokine ligand 5/C-C chemokine receptor 5 (CCL5/CCR5) axis and an increase in transient receptor potential ankyrin 1 (TRPA1) expression. Blocking the CCL5/CCR5 signaling or TRPA1 alleviated pain behaviors induced by PP2Cm deletion. Thus, targeting BCAA catabolism in DRG neurons may be a potential management strategy for pain sensitization.

Abstract Parkinson’s disease (PD) exhibits heterogeneity in terms of symptoms and prognosis, likely due to diverse neuroanatomical alterations. This study employs a contrastive deep learning approach to analyze Magnetic Resonance Imaging (MRI) data from 932 PD patients and 366 controls, aiming to disentangle PD-specific neuroanatomical alterations. The results reveal that these neuroanatomical alterations in PD are correlated with individual differences in dopamine transporter binding deficit, neurodegeneration biomarkers, and clinical severity and progression. The correlation with clinical severity is verified in an external cohort. Notably, certain proteins in the cerebrospinal fluid are strongly associated with PD-specific features, particularly those involved in the immune function. The most notable neuroanatomical alterations are observed in both subcortical and temporal regions. Our findings provide deeper insights into the patterns of brain atrophy in PD and potential underlying molecular mechanisms, paving the way for earlier patient stratification and the development of treatments to slow down neurodegeneration.

The construction of extraterrestrial bases has become a new goal in the active exploration of deep space. Among the construction techniques, in situ resource-based construction is one of the most promising because of its good sustainability and acceptable economic cost, triggering the development of various types of extraterrestrial construction materials. A comprehensive survey and comparison of materials from the perspective of performance was conducted to provide suggestions for material selection and optimization. Thirteen types of typical construction materials are discussed in terms of their reliability and applicability in extreme extraterrestrial environment. Mechanical, thermal and optical, and radiation-shielding properties are considered. The influencing factors and optimization methods for these properties are analyzed. From the perspective of material properties, the existing challenges lie in the comprehensive, long-term, and real characterization of regolith-based construction materials. Correspondingly, the suggested future directions include the application of high-throughput characterization methods, accelerated durability tests, and conducting extraterrestrial experiments.

In recent years, the deep integration of basic research and clinical translational research of nanotechnology and oncology has led to the emergence of a new branch, namely integrated nano-oncology. This is an emerging and important interdisciplinary field, which plays an irreplaceable role in the diagnosis, treatment, early warning, monitoring and prevention of tumors, and has become a new interdisciplinary frontier. Here main advances of integrated nano-oncology was reviewed, mainly included controlled preparation of nanomaterials, ultra-sensitive detection of tumor biomarkers, multi-functional nanoimaging probes and integrated diagnosis and treatment technology, innovative nano drugs and nano drug delivery system, DNA nanotechnology, RNA nanotechnology, nano self-assembly technology, nanosensors, intelligent nanorobots, nanotherapeutic machines. The terms, concepts, trends and challenges are also discussed with the aim of promoting the application of nanotechnology in integrated oncology and solving the scientific and key technical problems in basic and clinical translational research of cancer.

Heterogeneous drought stress (HED) is prevalent in drought-resistant practices such as deficit irrigation, root zone irrigation and strip intercropping. The mechanisms and improvement of crop drought resistance under HED are not fully understood. This study used double-root grafted Nandou 12 (ND12) soybean seedlings to simulate HED treatment under controlled conditions. Seedlings were transplanted into root cups with waterproof partitions to establish different soil moisture treatments: sufficient irrigation (SI) with 80 % soil moisture on both sides, HED with 80 % on one side and 40 % on the other, and homogeneous drought stress (HOD) with 60 % on both sides. The results indicated that soybean plants treated with HED exhibited healthier growth compared to those treated with HOD. Photosynthesis rate (Pn), stomatal conductance (cond.), transpiration rate (Tr), and relative water content (RWC) decreased by 10.24 %, 43.90 %, 152.66 %, and 8.69 % in HED-treated plants, respectively, but dry biomass increased by 3.38 %. Conversely, HOD conditions led to a significant decline in these parameters. Metabolomic and transcriptomic analyses revealed significant changes in the biosynthesis and signaling pathways of key phytohormones and metabolites, including abscisic acid (ABA), gibberellin (GA), jasmonic acid (JA), isoflavones, starch, and sugars. In HED-treated plants, GmNCED downregulation resulted in 54.22 % less ABA than HOD. GA levels increased under HED with upregulation of GmGA3OX1 and GmGA3OX2. JA content in HED-treated roots was 90.90 % higher than in HOD-treated roots. Isoflavones concentration including genistein (73.01 %), genistin (63.63 %), malonylgenistin (20.58 %), malonylgenistin (65 %), diadzin (38.15 %), and malonyldiadzin (47.61 %) levels, were significantly higher in HED-treated plants. Antioxidant enzyme activities indicated a 20 % increase in peroxidase (POD) activity under HED, while malondialdehyde (MDA) content was 27 % higher in HOD-treated plants, indicating greater oxidative stress. Chlorophyll content remained stable, and starch concentration increased by 33.33 % in HED-treated plants compared to HOD-treated plants. HED enhances phytohormonal responses and metabolic adjustments in soybean plants, boosting photosynthetic efficiency, antioxidant capabilities, growth, and drought resilience. This regulatory mechanism balances growth promotion and drought resistance, highlighting HED potential in improving crop resilience.

Background: Radiation-induced lung fibrosis (RILF) is a life-threatening complication of thoracic radiotherapy. Ferroptosis, a recently discovered type of cell death, is believed to contribute to RILF, though the associated mechanisms are unknown. This study aimed to investigate the potential mechanism of ferroptosis in RILF and examine the contribution of different cell types to ferroptosis during RILF progression. Methods: Histopathological changes in RILF lung tissue were assessed through H&E and Masson staining. IHC staining investigated ferroptosis markers (GPX4, ACSL4, NCOA4). Ferroptosis-related genes (FRG) and pathway scores were derived from RILF transcriptome microarray data. The sc-RNAseq analysis detected FRG score dynamics across cell types, validated by IF staining for PDGFR-α and ACSL4. Results: ACSL4 and NCOA4 protein levels were significantly higher and GPX4 lower in IR than control. FRG scores were positively correlated with fibrosis-related pathway scores in the RILF transcriptome data. FRG and ECM scores were concurrently upregulated in myofibroblasts. Enhanced co-staining of PDGFR-α and ACSL4 were observed in the fibrotic areas of RILF lungs. Conclusions: Our research indicated that in RILF, fibroblasts undergoing ferroptosis may release increased levels of ECM, potentially accelerating the progression of lung fibrosis. This finding presents ferroptosis as a potential therapeutic target in RILF.

BackgroundPrevious research has demonstrated an association between gut microbiota and immune status with the development of several diseases. However, whether these factors contribute to polyps remains unclear. This study aims to use Mendelian randomization (MR) to investigate the causal relationship between gut microbiota and 4 types of polyps (nasal, gallbladder, colon, and gastric polyps), as well as to analyze the mediating role of immune traits.MethodsThis study utilized large-scale GWAS meta-analyses of gut microbiota (MiBioGen Consortium), 731 immune traits, and 4 types of polyps (one from the FinnGen Consortium and three from the NBDC Human Database). Univariate MR with the inverse variance weighted (IVW) estimation method was employed as the primary analytical approach. A two-step MR analysis was performed to identify potential mediating immune traits. Additionally, multivariable MR approach based on Bayesian model averaging (MR-BMA) was employed to further prioritize gut microbiota and immune traits associated with polyp development.ResultsBased on IVW method in univariate MR analysis, we identified 39 gut microbial taxa and 135 immune traits significantly causally associated with at least one type of polyp. For nasal polyps, 13 microbial taxa and 61 immune traits were causally associated. After false discovery rate (FDR) correction, CD3 on Central Memory CD8+ T cells and CD3 on CD4 regulatory T cells remained significant. MR-BMA identified 4 gut microbial taxa and 4 immune traits as high priority. For gallbladder polyps, 9 microbial taxa and 30 immune traits were causally associated. MR-BMA identified 8 microbial taxa and 6 immune traits as higher importance. For colon polyps, 6 microbial taxa and 21 immune traits were causally associated. MR-BMA identified 4 microbial taxa and 3 immune traits as higher importance. For gastric polyps, 12 microbial taxa and 33 immune traits were causally associated. Actinobacteria remained significant after FDR correction, and MR-BMA identified 7 gut microbial taxa and 6 immune traits as high priority. We identified 16 causal pathways with mediator directions consistent with the direction of gut microbiome-polyp association. Of these, 6 pathways were associated with the mechanism of nasal polyps, 1 with gallbladder polyps, 2 with colon polyps, and 7 with gastric polyps.ConclusionsOur findings shed light on the causal relationships between gut microbiota, immune traits, and polyp development, underscoring the crucial roles of gut microbiota and immune status in polypogenesis. Furthermore, these findings suggest potential applications in polyp prevention, early screening, and the development of effective strategies to reduce polyp risk.

Flexible pressure sensors are lightweight and highly sensitive, making them suitable for use in small portable devices to achieve precise measurements of tiny forces. This article introduces a low-cost and easy-fabrication strategy for piezoresistive flexible pressure sensors. By embedding silver nanowires into a polydimethylsiloxane layer with micro-pyramids on its surface, a flexible pressure sensor is created that can detect low pressure (17.3 Pa) with fast response (

This paper evaluates the macroeconomic effects of monetary policy for a central bank digital currency rule with traditional monetary policy in an open environment. We build a dynamic stochastic general equilibrium small open model economy with interest-bearing central bank digital currency assets. The redistribution of asset holdings and the change in asset price are the two pathways through which a retail central bank digital currency rule under the traditional monetary policy affects the macroeconomy. Fiat's digital and traditional monetary policies complement one another in lowering macroeconomic fluctuations. As a result, the real exchange rate, current accounts, and consumption are more stable in transmitting foreign shocks. These results occur when price-based or quantitative-based fiat digital monetary policy parallels traditional price-based monetary policy.

BackgroundPortal vein tumor thrombus (PVTT) is a major risk factor of recurrence of hepatocellular carcinoma (HCC) after hepatectomy. Whether postoperative adjuvant immunotherapy and molecular targeted therapy (I-O and MTT) is effective in reducing the risk of recurrence of HCC with minimal portal invasion after hepatectomy and improving prognosis is unknown.MethodsWe collected the data of HCC with Vp1 or Vp2 PVTT patients who underwent hepatectomy at our center between January 2019 and June 2022 from the hospital database. We utilized propensity score matching (PSM) to establish a 1:1 match between the postoperative group treated with I-O and MTT and the postoperative group without I-O and MTT. To compare the recurrence-free survival (RFS) and overall survival (OS) between the two groups, we employed the Kaplan-Meier method. Additionally, we conducted Cox regression analysis to identify the prognostic factors that influence patient prognosis. To account for different high-risk factors, subgroup analyses were carried out.ResultsAmong the 189 patients included in the study, 42 patients received postoperative adjuvant I-O and MTT. After PSM, the 1, 2-years RFS were 59.2%, 21.3% respectively in the I-O and MTT group and 40.8%, 9.6% respectively in the non-I-O and MTT group. The median RFS was 13.2 months for the I-O and MTT group better than 7.0 months for the non-I-O and MTT group (P = 0.028). 1, 2-years OS were 89.8%, 65.8% respectively in the I-O and MTT group and 42.4%, 27.7% respectively in the non-I-O and MTT group. The median OS was 23.5 months for the I-O and MTT group better than 17.2 months for the non-I-O and MTT group (P = 0.027). Multivariate analysis showed that postoperative adjuvant I-O and MTT was a prognostic protective factor associated with OS and RFS. The most frequent AE observed in this study was pruritus, and rare AEs included decreased platelet, hypothyroidism, proteinuria, myocarditis and hypoadrenocorticism. The incidence of GRADE ≥3 AE with no deaths recorded.ConclusionThe study suggested that postoperative adjuvant I-O and MTT strategy was beneficial to improve the prognosis of HCC patients with PVTT patients, while the therapy was safe and reliable.

Abstract Background The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). Methods 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. Results Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P

Abstract Fast computational ghost imaging with high quality and ultra-high-definition resolution reconstructed images has important application potential in target tracking, biological imaging and other fields. However, as far as we know, the resolution (pixels) of the reconstructed image is related to the number of measurements. And the limited resolution of reconstructed images at low measurement times hinders the application of computational ghost imaging. Therefore, in this work, a new computational ghost imaging method based on saliency variable sampling detection is proposed to achieve high-quality imaging at low measurement times. This method physically variable samples the salient features and realizes compressed detection of computational ghost imaging based on the salient periodic features of the bucket detection signal. Numerical simulation and experimental results show that the reconstructed image quality of our method is similar to the compressed sensing method at low measurement times. Even at 500 (sampling rate $$0.76\%$$ 0.76 % ) measurement times, the reconstructed image of the method still has the target features. Moreover, the $$2160\times 4096$$ 2160 × 4096 (4K) pixels ultra-high-definition resolution reconstructed images can be obtained at only a sampling rate of $$0.11\%$$ 0.11 % . This method has great potential value in real-time detection and tracking, biological imaging and other fields.

Abstract Brain structural changes in Parkinson’s disease (PD) are progressive throughout the disease course. Changes in surface morphology with disease progression remain unclear. This study aimed to assess the volumetric and shape changes of the subcortical nuclei during disease progression and explore their association with clinical symptoms. Thirty-four patients and 32 healthy controls were enrolled. The global volume and shape of the subcortical nuclei were compared between patients and controls at baseline. The volume and shape changes of the subcortical nuclei were also explored between baseline and 2 years of follow-up. Association analysis was performed between the volume of subcortical structures and clinical symptoms. In patients with PD, there were significantly atrophied areas in the left pallidum and left putamen, while in healthy controls, the right putamen was dilated compared to baseline. The local morphology of the left pallidum was correlated with Mini Mental State Examination scores. The left putamen shape variation was negatively correlated with changes in Unified Parkinson’s Disease Rating Scale PART III scores. Local morphological atrophy of the putamen and pallidum is an important pathophysiological change in the development of PD, and is associated with motor symptoms and cognitive status in patients with PD.

Abstract Background Bladder cancer (BC) is a very common urinary tract malignancy that has a high incidence and lethality. In this study, we identified BC biomarkers and described a new noninvasive detection method using serum and urine samples for the early detection of BC. Methods Serum and urine samples were retrospectively collected from patients with BC (n = 99) and healthy controls (HC) (n = 50), and the expression levels of 92 inflammation-related proteins were examined via the proximity extension analysis (PEA) technique. Differential protein expression was then evaluated by univariate analysis (p

Abstract Due to their extensive microporous structure, metal‐organic frameworks (MOFs) find widespread application in constructing modification layers, functioning as ion sieves. However, the modification layers prepared by existing methods feature gaps between MOFs that are noticeably larger than the inherent MOF pore dimensions. Polysulfides and lithium ions unavoidably permeate through these gaps, hindering the full exploitation of the structural advantages. Herein, an ultrathin (20 nm) and crack‐free MOF film is formed on the separator by atomic layer deposition for the first time. Based on the separator, the mechanism of different MOF layers has been verified by phase field simulation and in situ Raman spectroscopy. The results accurately prove that the MOF particle layer can relieve the shuttle of polysulfides, but it does not have the effect of homogenizing lithium ions. Only the ultrathin and crack‐free MOF film with proper pore size can act as the ion sieve for both polysulfides and lithium ions. As a result, under the test condition of 2 mA cm−2–2 mAh cm−2, the overpotential of the Li/Li symmetric battery is only 18 mV after 2500 h. The capacity retention rate of the lithium–sulfur battery is 95.6% after 500 cycles and 80% after 1000 cycles at 2 C.

Abstract Background Trigeminal nerve injury is one of the most serious complications in oral clinics, and the subsequent chronic orofacial pain is a consumptive disease. Increasing evidence demonstrates long non-coding RNAs (lncRNAs) play an important role in the pathological process of neuropathic pain. This study aims to explore the function and mechanism of LncRNA Anxa10-203 in the development of orofacial neuropathic pain. Methods A mouse model of orofacial neuropathic pain was established by chronic constriction injury of the infraorbital nerve (CCI-ION). The Von Frey test was applied to evaluate hypersensitivity of mice. RT-qPCR and/or Western Blot were performed to analyze the expression of Anxa10-203, DHX30, and MC1R. Cellular localization of target genes was verified by immunofluorescence and RNA fluorescence in situ hybridization. RNA pull-down and RNA immunoprecipitation were used to detect the interaction between the target molecules. Electrophysiology was employed to assess the intrinsic excitability of TG neurons (TGNs) in vitro. Results Anxa10-203 was upregulated in the TG of CCI-ION mice, and knockdown of Anxa10-203 relieved neuropathic pain. Structurally, Anxa10-203 was located in the cytoplasm of TGNs. Mechanistically, Mc1r expression was positively correlated with Anxa10-203 and was identified as the functional target of Anxa10-203. Besides, Anxa10-203 recruited RNA binding protein DHX30 and formed the Anxa10-203/DHX30 complex to enhance the stability of Mc1r mRNA, resulting in the upregulation of MC1R, which contributed to the enhancement of the intrinsic activity of TGNs in vitro and orofacial neuropathic pain in vivo. Conclusions LncRNA Anxa10-203 in the TG played an important role in orofacial neuropathic pain and mediated mechanical allodynia in CCI-ION mice by binding with DHX30 to upregulate MC1R expression. Graphical Abstract The up-regulated lncRNA Anxa10-203 in the trigeminal ganglion of CCI-ION mice interacts with DHX30 to contribute to the excitability of TG neurons and orofacial pain by enhancing Mc1r mRNA stability.

Abstract Adipose-derived stem cells (ASCs) are a critical adult stem cell subpopulation and are widely utilized in the fields of regenerative medicine and stem cell research due to their abundance, ease of harvest, and low immunogenicity. ASCs, which are homologous with skin by nature, can treat immune-related skin diseases by promoting skin regeneration and conferring immunosuppressive effects, with the latter being the most important therapeutic mechanism. ASCs regulate the immune response by direct cell–cell communication with immune cells, such as T cells, macrophages, and B cells. In addition to cell–cell interactions, ASCs modulate the immune response indirectly by secreting cytokines, interleukins, growth factors, and extracellular vesicles. The immunomodulatory effects of ASCs have been exploited to treat many immune-related skin diseases with good therapeutic outcomes. This article reviews the mechanisms underlying the immunomodulatory effects of ASCs, as well as progress in research on immune-related skin diseases.

Abstract Hail, a highly destructive weather phenomenon, necessitates critical identification and forecasting for the protection of human lives and properties. The identification and forecasting of hail are vital for ensuring human safety and safeguarding assets. This research proposes a deep learning algorithm named Dual Attention Module EfficientNet (DAM-EfficientNet), based on EfficientNet, for detecting hail weather conditions. DAM-EfficientNet was evaluated using FY-4A satellite imagery and real hail fall records, achieving an accuracy of 98.53% in hail detection, a 97.92% probability of detection, a false alarm rate of 2.08%, and a critical success index of 95.92%. DAM-EfficientNet outperforms existing deep learning models in terms of accuracy and detection capability, with fewer parameters and computational needs. The results validate DAM-EfficientNet’s effectiveness and superior performance in hail weather detection. Case studies indicate that the model can accurately forecast potential hail-affected areas and times. Overall, the DAM-EfficientNet model proves to be effective in identifying hail weather, offering robust support for weather disaster alerts and prevention. It holds promise for further enhancements and broader application across more data sources and meteorological parameters, thereby increasing the precision and timeliness of hail forecasting to combat hail disasters and boost public safety.

Abstract Background USP54, a ubiquitin-specific protease in the deubiquitinase (DUB) family, facilitates the malignant progression of several types of cancer. However, the role of USP54 in prostate cancer (PCa), especially castration-resistant prostate cancer (CRPC), remains unknown. Methods We established the CRPC LNCaP-AI cell line from the hormone-sensitive prostate cancer (HSPC) LNCaP cell line. RNA-Seq was utilized to explore DUB expression levels in LNCaP and LNCaP-AI. USP54 was knocked down, and its effects on cell growth were evaluated in vitro and in vivo. Bioinformatics analyses were conducted to explore signaling pathways affected by USP54 in PCa. Quantitative polymerase chain reaction was used to confirm key signaling pathways involved. Results USP54 was the most strongly upregulated DUB in LNCaP-AI cells compared with LNCaP cells. USP54 levels were higher in PCa than in normal tissues. USP54 silencing suppressed the proliferation of PCa cell lines, both in vitro and in vivo. USP54 expression was positively correlated with the androgen receptor (AR) signaling level in PCa samples, and USP54 knockdown inhibited AR signaling in PCa cells. Conclusions USP54 was upregulated during HSPC progression to CRPC. USP54 depletion suppressed CRPC cell proliferation both in vitro and in vivo. USP54 may facilitate PCa progression by regulating AR signaling.

The G1/S transition is crucial for regulating the initiation of cell division and is highly conserved across eukaryotes. This phase of the cell cycle involves intricate transcriptional controls that are essential for understanding cell proliferation dynamics. The G1/S transition integrates diverse intracellular and extracellular signals, including growth factors and cell sizes. Saccharomyces cerevisiae, an important model organism, plays an integral role in unveiling the regulatory mechanisms of the G1/S transition. Recent studies on the G1/S transition in both yeast and vertebrates have demonstrated a direct correlation between dysregulation of the G1/S transition and the development of cancer. This review explores the G1/S transition regulatory network and its association with cancer formation, providing a theoretical foundation for future research in fundamental cell cycle dynamics and cancer.

This case report describes a 3-month-old male infant diagnosed with severe mitral stenosis (MS) and mitral regurgitation (MR) by transthoracic echocardiography. The male infant initially underwent complex mitral valve repair surgery. However, postoperative deterioration occurred with hemodynamic instability and shock, necessitating multiple resuscitation efforts and ultimately requiring support from Extracorporeal Membrane Oxygenation (ECMO). Given the serious conditions, the cardiac team decided to perform mitral valve replacement with a fresh allograft aortic valve. Postoperatively, the patient was promptly weaned off ECMO support, and the valve demonstrated sustained functionality throughout the long-term follow-up.

Acute myeloid leukemia (AML) is a common hematological malignancy with overall poor prognosis. Exploring novel targets is urgent and necessary to improve the clinical outcome of relapsed and refractory (RR) AML patients. Through clinical specimens, animal models and cell-level studies, we explored the specific mechanism of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 (HMGCS1) in AML and the mechanism of targeting HMGCS1 to attenuate cell proliferation, increase chemotherapy sensitivity and improve the occurrence and development of AML. Here, we reveal that HMGCS1 is overexpressed in RR patients and negatively related to overall survival (OS). Knocking out HMGCS1 in AML cells attenuated cell proliferation and increased chemotherapy sensitivity, while stable overexpression of HMGCS1 had the opposite effects. Mechanistically, we identified that knockout of HMGCS1 suppressed mitogen-activated protein kinase (MAPK) pathway activity, while overexpression of HMGCS1 could remarkably enhance the pathway. U0126, a MEK1 inhibitor, offset the effects of HMGCS1 overexpression, indicating that HMGCS1 promotes RR AML through the MAPK pathway. Further, we verified that hymeglusin, a specific inhibitor of HMGCS1, decreases cell growth both in AML cell lines and primary bone marrow cells of AML patients. Furthermore, combination of hymeglusin and the common chemotherapeutic drug cytarabine and adriamycin (ADR) had synergistic toxic effects on AML cells. Our study demonstrates the important role of HMGCS1 in AML, and targeting this protein is promising for the treatment of RR AML.

The adult mammalian cardiomyocyte has a limited capacity for self-renewal, which leads to the irreversible heart dysfunction and poses a significant threat to myocardial infarction patients. In the past decades, research efforts have been predominantly concentrated on the cardiomyocyte proliferation and heart regeneration. However, the heart is a complex organ that comprises not only cardiomyocytes but also numerous noncardiomyocyte cells, all playing integral roles in maintaining cardiac function. In addition, cardiomyocytes are exposed to a dynamically changing physical environment that includes oxygen saturation and mechanical forces. Recently, a growing number of studies on myocardial microenvironment in cardiomyocyte proliferation and heart regeneration is ongoing. In this review, we provide an overview of recent advances in myocardial microenvironment, which plays an important role in cardiomyocyte proliferation and heart regeneration.

Efficient, non-destructive cabbage harvesting is crucial for preserving its flavor and quality. Current cabbage harvesting mainly relies on mechanized automatic picking methods. However, a notable deficiency in most existing cabbage harvesting devices is the absence of a root posture recognition system to promptly adjust the root posture, consequently impacting the accuracy of root cutting during harvesting. To address this issue, this study introduces a cabbage root posture recognition method that combines deep learning with traditional image processing algorithms. Preliminary detection of the main root Region of Interest (ROI) areas of the cabbage is carried out through the YOLOv5s deep learning model. Subsequently, traditional image processing methods, the Graham algorithm, and the method of calculating the minimum circumscribed rectangle are employed to specifically detect the inclination angle of cabbage roots. This approach effectively addresses the difficulty in calculating the inclination angle of roots caused by occlusion from outer leaves. The results demonstrate that the precision and recall of this method are 98.7 % and 98.6 %, respectively, with an average absolute error of 0.80° and an average relative error of 1.34 % in posture. Using this method as a reference for mechanical harvesting can effectively mitigate cabbage damage rates.

Abstract Diagnosis and stratification of prostate cancer (PCa) patients using the prostate‐specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness of tissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label‐free LC‐MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from different PCa stages through parallel reaction monitoring‐based targeted proteomics, western blotting, and ELISA. Additionally, a tissue microarray containing cancerous and noncancerous tissues is screened to provide additional evidence of selected sEV proteins associated with cancer origin. Results indicate that sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localised PCa patients and control subjects, while sEV protein Histone H4 is highly expressed in human urine of high‐risk PCa patients compared to low‐risk PCa patients and control subjects. These two sEV proteins demonstrate higher specificity and sensitivity than the PSA test and show promise for metastatic PCa diagnosis, progression monitoring, and risk stratification.

Abstract The low translocation rate of stem assimilates and lodging under high nitrogen conditions are major factors limiting the realization of the yield potential of rice. The objectives of this study were to (1) determine the characteristics of stem nonstructural carbohydrates (NSCs) translocation and lodging resistance in different types of rice varieties and (2) elucidate the responses of stem NSCs translocation and lodging resistance to reduced nitrogen (RN) input. Field experiments were conducted using four types of rice varieties with two nitrogen levels, including normal nitrogen (NN, namely, farmer's practice, 225 kg N ha−1 for indica conventional and indica hybrid rice and 300 kg N ha−1 for japonica conventional and indica–japonica hybrid rice in Jiangsu Province, China) and 20% RN (180 and 240 kg N ha−1, respectively). The results showed that there were significant differences in the stem NSCs translocation and lodging index of the basal stem among different types of varieties; indica hybrid rice was the highest, followed by indica conventional rice and indica–japonica hybrid rice, while japonica conventional rice was the lowest. The high activities of α‐amylase, β‐amylase, and sucrose phosphate synthase may contribute to high stem NSCs translocation. Correlation analysis revealed that NSCs translocation was significantly positively correlated with 1000‐grain weight, grain yield, and lodging index, while it was significantly negatively correlated with dry weight/length, dry weight/volume, and bending stress of the basal stem. Compared with NN, RN significantly improved NSCs translocation and had no significant effect on the lodging resistance‐related traits of the basal stem or grain yield. Therefore, this research indicates that a 20% reduction in nitrogen input can maintain grain yield by enhancing stem assimilate translocation without lodging resistance reduction and consequently synergizing nitrogen reduction, high yield, and lodging resistance.

Background: Whether there is hypothalamic degeneration in Parkinson's disease (PD) and its association with clinical symptoms and pathophysiological changes remains controversial. Objectives: We aimed to quantify microstructural changes in hypothalamus using a novel deep learning-based tool in patients with PD and those with probable rapid-eye-movement sleep behavior disorder (pRBD). We further assessed whether these microstructural changes associated with clinical symptoms and free thyroxine (FT4) levels. Methods: This study included 186 PD, 67 pRBD, and 179 healthy controls. Multi-shell diffusion MRI were scanned and mean kurtosis (MK) in hypothalamic subunits were calculated. Participants were assessed using Unified Parkinson's Disease Rating Scale (UPDRS), RBD Questionnaire-Hong Kong (RBDQ-HK), Hamilton Depression Rating Scale (HAMD), and Activity of Daily Living (ADL) Scale. Additionally, a subgroup of PD (n = 31) underwent assessment of FT4. Results: PD showed significant decreases of MK in anterior-superior (a-sHyp), anterior-inferior (a-iHyp), superior tubular (supTub), and inferior tubular hypothalamus when compared with healthy controls. Similarly, pRBD exhibited decreases of MK in a-iHyp and supTub. In PD group, MK in above four subunits were significantly correlated with UPDRS-I, HAMD, and ADL. Moreover, MK in a-iHyp and a-sHyp were significantly correlated with FT4 level. In pRBD group, correlations were observed between MK in a-iHyp and UPDRS-I. Conclusions: Our study reveals that microstructural changes in the hypothalamus are already significant at the early neurodegenerative stage. These changes are associated with emotional alterations, daily activity levels, and thyroid hormone levels.

BackgroundDexmedetomidine has been used as a perineural local anesthetic (LA) adjuvant to facilitate the potency of erector spinal plane block (ESPB). This quantitative review aimed to evaluate whether perineural dexmedetomidine for ESPB can improve the effects of analgesia compared to LA alone.MethodsRandomized controlled trials (RCTs) that investigated the addition of dexmedetomidine to LA compared to LA alone in ESPB were included. The pain scores, duration of sensory block, the time to first analgesia requirement, postoperative morphine consumption, rescue analgesia, and dexmedetomidine-related side effects were analyzed and combined using random-effects models.ResultsA total of 823 patients from 13 RCTs were analyzed. Dexmedetomidine was used at the concentration of 0.5 μg/kg in three trials and 1 μg/kg in nine trials, and both in one trial. Both concentrations of dexmedetomidine perineurally administrated significantly reduced the rest VAS scores postoperatively at 12 h (0.5 μg/kg dexmedetomidine: MD = −0.86; 95% CI: −1.59 to −0.12; p = 0.02; 1 μg/kg dexmedetomidine: MD = −0.49; 95% CI: −0.83 to −0.16; p = 0.004), and 24 h (0.5 μg/kg dexmedetomidine: MD = −0.43; 95% CI: −0.74 to −0.13; p = 0.005; 1 μg/kg dexmedetomidine: MD = −0.62; 95% CI: −0.84 to −0.41; p

Accurate identification of rice ears is crucial for assessing rice yield. Present research mainly relies on single-scale image data for rice ears detection and counting. However, these approaches are susceptible to misdetection and omission due to the intricate environmental conditions in fields. The combination of multi-source images can better overcome the limitations of single-scale images. In this study, based on the YOLOv5s target detection algorithm, a method for rice ears detection and counting applicable to multi-source images is proposed by integrating image data collected by cell phones and UAVs during the rice heading and maturity periods. The proposed method introduces Attention-based Intrascale Feature Interaction (AIFI) to reconstruct the backbone feature extraction network, optimizing feature expression interaction and enhancing handling of the model of advanced semantic information. Additionally, Simplify Optimal Transport Assignment (SimOTA) is employed to achieve a more refined label assignment strategy, thereby optimizing detection performance of the model and addressing difficulties in detecting multiple targets in high-density rice ears environments. Finally, Channel-wise Knowledge Distillation for Dense Prediction (CWD) is utilized to enhance the performance of the model in dense prediction tasks by transferring knowledge between different channels. The experimental results demonstrated good performance of the model on datasets comprising rice at the heading and maturity stages, achieving Precision, Recall, and mAP values of 93%, 85.3%, and 90.3%, respectively. The coefficients of determination (R $^{2}$ ) for the linear fit between test results and the actual statistical results of the model were 0.91, 0.91, 0.90, and 0.88, respectively. The proposed model performs well in the mixed dataset and can be utilized more effectively for accurate identification and counting of rice ears.

Abstract Objective To compare the clinical effects of intramedullary elastic reduction of the “de-sharpened Kirschner wire and traditional three-dimensional manipulation in the treatment of Gartland type III posterolateral supracondylar fracture of the humerus in children. Methods A retrospective cohort analysis was made on 106 cases of Gartland type III posterolateral supracondylar fracture of the humerus treated in the Department of Orthopaedics of a Children’s Hospital from March 2020 to March 2022. According to different surgical technology, the patients were divided into two groups: intramedullary elastic reduction of the de-sharpened Kirschner wire group (experimental group, n = 50) and traditional three-dimensional manipulation group (control group, n = 56). The surgical operating time, intraoperative fluoroscopy times, postoperative Baumann angle changes, postoperative elbow function Flynn score, and complications were collected and compared between the two groups. Results All the enrolled cases underwent surgery successfully and were followed-up at least 6 months. The surgical operating time of the experimental group was 32.88 ± 3.69 min and that of the control group was 45.56 ± 10.13 min, and the difference was statistically significant (P 0.5). There were no complications such as osteomyelitis, compartment syndrome, iatrogenic vascular and nerve injury, and myositis ossificans in either group. Conclusions Good functional outcome can be obtained with both intramedullary elastic reduction of the de-sharpened Kirschner wire and traditional three-dimensional manipulation for Gartland type III posterolateral displaced supracondylar fracture of the humerus in children; however, the former does not need repeated manipulation, and the operation time is shorter, the number of intraoperative fluoroscopy is less, and the recovery of the Baumann angle is better.

Abstract Current diagnostic tools for prostate cancer (PCa) diagnosis and risk stratification are insufficient. The hidden onset and poor efficacy of traditional therapies against metastatic PCa make this disease a heavy burden in global men’s health. Prostate cancer-derived extracellular vesicles (PCDEVs) have garnered attention in recent years due to their important role in communications in tumor microenvironment. Recent advancements have demonstrated PCDEVs proteins play an important role in PCa invasion, progression, metastasis, therapeutic resistance, and immune escape. In this review, we briefly discuss the applications of sEV proteins in PCa diagnosis and prognosis in liquid biopsy, focus on the roles of the PCa-derived small EVs (sEVs) proteins in tumor microenvironment associated with cancer progression, and explore the therapeutic potential of sEV proteins applied for future metastatic PCa therapy. Graphical Abstract

Abstract Objective Stroke is a rare but fatal complication of advanced cancer with Trousseau syndrome, especially as initial symptoms. Here, we report the clinical characteristics, treatment, and prognosis of patients with non-small cell lung cancer (NSCLC) who initially presenting with acute multiple cerebral infarction. Methods The clinical characteristics, imaging, treatment, and oncological outcomes of 10 patients diagnosed with Trousseau syndrome and NSCLC between 2015 and 2021 at Guangdong Sanjiu Brain Hospital were retrospectively collected and analyzed. The clinical course of two typical cases were presented. Results All 10 patients with pathologically confirmed lung adenocarcinoma initially presented with neurological symptoms, including hemiplegic paralysis (7 patients, 70%), dizziness (5 patients, 50%), and unclear speech (3 patients, 30%). The median age was 63.5 years. Eight and two cases were stage III and IV, respectively, at the initial diagnosis. Five patients underwent driver gene testing, revealing three patients with EGFR-sensitive mutations, one patient with ALK fusion, and one patient with wild-type EGFR. All 10 patients received antiplatelet therapy, and six patients subsequently received anti-cancer treatment. The median overall survival of the patients was 8.5 months (95% confidence interval) and 1-year survival rate was 57.1%. Patients who received antitumor treatment, especially those harboring driver gene mutations and received tyrosine kinase inhibitors, had better neurological symptom recovery and superior oncological prognosis (median overall survival, not reached versus 7.4 months, p = 0.038). Conclusion Trousseau syndrome, presenting as multiple cerebral infarctions, is a rare complication of lung adenocarcinoma. Both antiplatelet and antitumor treatment are recommended to achieve better neurological recovery and oncological prognosis in these patients.

Abstract Primary liver cancer (PLC) poses a leading threat to human health, and its treatment options are limited. Meanwhile, the investigation of homogeneity and heterogeneity among PLCs remains challenging. Here, using single-cell RNA sequencing, spatial transcriptomic and bulk multi-omics, we elaborated a molecular architecture of 3 PLC types, namely hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC). Taking a high-resolution perspective, our observations revealed that CHC cells exhibit internally discordant phenotypes, whereas ICC and HCC exhibit distinct tumor-specific features. Specifically, ICC was found to be the primary source of cancer-associated fibroblasts, while HCC exhibited disrupted metabolism and greater individual heterogeneity of T cells. We further revealed a diversity of intermediate-state cells residing in the tumor-peritumor junctional zone, including a congregation of CPE+ intermediate-state endothelial cells (ECs), which harbored the molecular characteristics of tumor-associated ECs and normal ECs. This architecture offers insights into molecular characteristics of PLC microenvironment, and hints that the tumor-peritumor junctional zone could serve as a targeted region for precise therapeutical strategies.

Cyclophosphamide is commonly used in the treatment of various cancers and autoimmune diseases, while concurrently imposing substantial toxicity on the bladder, frequently manifesting hemorrhagic cystitis. Intravesical interventions, such as hyaluronic acid supplementation, present a therapeutic strategy to reinstate bladder barrier function and alleviate the effects of metabolic toxicants. However, it remains a great challenge to achieve efficient cyclophosphamide-induced hemorrhagic cystitis (CHC) management with accelerated tissue repair owing to the low wet-adhesion, poor hemostasis, and acute inflammatory responses. To address these issues, a hemostatic and anti-inflammatory hydrogel adhesive of chitosan methylacryloyl/silk fibroin methylacryloyl (CHMA/SFMA) is developed for promoting the healing of CHC. The obtained hydrogels show a high adhesive strength of 26.21 N/m with porcine bladder, facilitating the rapid hemostasis within 15 s, and reinstate bladder barrier function. Moreover, this hydrogel adhesive promotes the proliferation and aggregation of SV-HUC-1 and regulates macrophage polarization. Implanting the hydrogels into CHC bladders of a SD rat model, they not only can be completely biodegraded in 14 days, but also effectively control hematuria and inflammation, and accelerate angiogenesis, thereby significantly promote the healing of bladder injury. Overall, CHMA/SFMA hydrogels exhibit rapid hemostasis for treating CHC and accelerate muscle tissue repair via angiogenesis and inflammation amelioration, which may provide a new path for managing severe hemorrhagic cystitis in the clinics.

Abstract Increasing the application of nitrogen fertilizer is the main approach to increase rice production, but it also brings problems of environmental pollution and increases agricultural production costs. Cultivating high‐yielding and high nitrogen use efficiency (NUE) rice varieties is an important approach to solving this problem. The rice varieties carrying dep1 (dense and erect panicle 1) have both high grain yield and high NUE. However, their plant traits have not been fully explored. In this study, two rice near‐isogenic lines carrying dep1 (NIL‐DEP1 and NIL‐dep1) were grown in paddy fields under 0, 120 and 270 kg N ha−1. We analyzed agronomic traits of panicle type, plant type, leaves and roots, and physiological traits of vascular bundles, photosynthetic rate and carbon and nitrogen transport. The results showed that the NIL‐dep1 exhibited higher grain yield and NUE than NIL‐DEP1, mainly due to the higher spikelet number per panicle, grain filling percentage and dry matter production. Compared with NIL‐DEP1, NIL‐dep1 had improved flag leaf morpho–physiological traits, including erect flag leaves, greater leaf thickness and specific leaf weight, higher root dry weight, root length, root volume and root surface area, and a better canopy structure, as reflected by a lower light interception percent and canopy extinction coefficient, leading to better photosynthetic performance and dry matter production. In addition, NIL‐dep1 exhibited better vascular bundle traits of peduncle and enhanced dry matter, stem carbon and nitrogen translocation during grain filling. In conclusion, NIL‐dep1 had high grain yield and NUE by improved agronomic and physiological traits and increasing carbon and nitrogen translocation during grain filling. These traits mentioned above could be used to select and breed high grain yield with high NUE rice varieties.

The compaction quality of rockfill materials plays a pivotal role in ensuring the stability and durability of runway structures. However, traditional assessment methods relying on limited random sampling may lack representativeness for the entire construction site and overlook potential areas of insufficient compaction. Addressing this challenge, this paper employs the dynamic deformation modulus (EVD), a rapid and nondestructive testing method, to assess the compaction quality of runway rockfill. Subsequently, this paper propose a 3D Conditional Random Field (CRF) model based on EVD to simulate the uncertain spatial distribution of rockfill compaction quality, allowing for the estimation of the overall construction area's compaction quality with a limited number of sample points. The validity of the model is demonstrated through a case study involving a runway expansion project. Additionally, three critical construction factors--namely, measurement points, compaction passes, and compaction materials--are analyzed throughout the construction process. This analysis provides managers with valuable insights and decision-making tools to promptly evaluate the quality of compaction areas, ensuring the stability and durability of the runway.

Background: Parkinson's disease (PD) patients exhibit an imbalance between neuronal activity and perfusion, referred to as abnormal neurovascular coupling (NVC). Nevertheless, the underlying molecular mechanism and how levodopa, the standard treatment in PD, regulates NVC is largely unknown. Material and methods: A total of 52 drug-naïve PD patients and 49 normal controls (NCs) were enrolled. NVC was characterized in vivo by relating cerebral blood flow (CBF) and amplitude of low-frequency fluctuations (ALFF). Motor assessments and MRI scanning were conducted on drug-naïve patients before and after levodopa therapy (OFF/ON state). Regional NVC differences between patients and NCs were identified, followed by an assessment of the associated receptors/transporters. The influence of levodopa on NVC, CBF, and ALFF within these abnormal regions was analyzed. Results: Compared to NCs, OFF-state patients showed NVC dysfunction in significantly lower NVC in left precentral, postcentral, superior parietal cortex, and precuneus, along with higher NVC in left anterior cingulate cortex, right olfactory cortex, thalamus, caudate, and putamen (P-value

ObjectiveThere is currently no non-invasive examination that can fully determine the diagnosis of osteomyelitis. SPECT/CT tomographic fusion imaging can provide both local metabolic activity and anatomical information to determine the condition and location. This study evaluates the diagnostic efficacy of 99mTc-MDP SPECT/CT in bone infections, compared to MRI.MethodsIn this multicenter retrospective study, 363 patients with suspected bone and joint infections or osteomyelitis were included. Participants underwent 99mTc-MDP SPECT/CT and/or MRI examinations, supplemented by pathogenic bacterial cultures and histopathological analysis.ResultsOnly SPECT/CT was tested in 169 patients, and only MRI was used in 116. 78 people have implemented both inspections and have detailed information. The diagnostic sensitivity and specificity of SPECT/CT for infection were 96% and 92% respectively, with an accuracy of 96%. For MRI, these figures were 88%, 84%, and 87% respectively.ConclusionThis represents the largest global study to date evaluating osteomyelitis and bone infection diagnosis using 99mTc-MDP SPECT/CT tomographic fusion imaging. The findings indicate that 99mTc-MDP SPECT/CT fusion imaging offers superior diagnostic accuracy compared to MRI. This is particularly evident in cases involving metallic implants and chronic infections. 99mTc-MDP SPECT/CT fusion imaging emerges as a highly suitable non-invasive diagnostic modality, facilitating enhanced clinical follow-up and treatment.

Abstract Background Halophiles possess several unique properties and have broad biotechnological applications including industrial biotechnology production. Halomonas spp., especially Halomonas bluephagenesis, have been engineered to produce various biopolyesters such as polyhydroxyalkanoates (PHA), some proteins, small molecular compounds, organic acids, and has the potential to become a chassis cell for the next-generation of industrial biotechnology (NGIB) owing to its simple culture, fast growth, contamination-resistant, low production cost, and high production value. An efficient genome editing system is the key for its engineering and application. However, the efficiency of the established CRISPR-Cas-homologous recombination (HR) gene editing tool for large DNA fragments was still relatively low. In this study, we firstly report a CRISPR-Cas9 gene editing system combined with a non-homologous end joining (NHEJ) repair system for efficient large DNA fragment deletion in Halomonas bluephagenesis. Results Three different NHEJ repair systems were selected and functionally identified in Halomonas bluephagenesis TD01. The NHEJ system from M. tuberculosis H37Rv (Mt-NHEJ) can functionally work in H. bluephagenesis TD01, resulting in base deletion of different lengths for different genes and some random base insertions. Factors affecting knockout efficiencies, such as the number and position of sgRNAs on the DNA double-strands, the Cas9 protein promoter, and the interaction between the HR and the NHEJ repair system, were further investigated. Finally, the optimized CRISPR-Cas9-NHEJ editing system was able to delete DNA fragments up to 50 kb rapidly with high efficiency of 31.3%, when three sgRNAs on the Crick/Watson/Watson DNA double-strands and the arabinose-induced promoter Para for Cas9 were used, along with the background expression of the HR repair system. Conclusions This was the first report of CRISPR-Cas9 gene editing system combined with a non-homologous end joining (NHEJ) repair system for efficient large DNA fragment deletion in Halomonas spp. These results not only suggest that this editing system is a powerful genome engineering tool for constructing chassis cells in Halomonas, but also extend the application of the NHEJ repair system.

Abstract Objective Previous studies have proposed that food intakes are associated with the risk of urolithiasis. Here, we conducted a two-sample Mendelian randomization (MR) study to evaluate the causal effects of different food intakes on urolithiasis. Methods Independent genetic variants associated with different food intakes at a genome-wide significant level were selected from summary-level statistics of genome-wide association studies from the UK Biobank. The association of these instrumental variables with urolithiasis was studied in a cohort from FinnGen Consortium. Results Among the 15 studied food intake exposures, tea intake (odds ratio [OR] = 0.433, 95% confidence interval [CI] = 0.281–0.667, p value = 1.470 × 10–4) and fresh fruit intake (OR = 0.358, 95% CI = 0.185–0.694, p value = 0.002) were found to significantly reduce the risk of the calculus of kidney and ureter. The association remained consistent in the sensitivity analyses. After adjusting for the effects of vitamin D and vitamin C, fresh fruit intake remained the reverse causal association with the calculus of kidney and ureter. Conclusions Genetically proxied fresh fruit intake is causally associated with a reduced risk of the calculus of kidney and ureter.

Abstract Objective To determine whether white matter hyperintensity (WMH) volumes in specific regions are associated with Parkinson's disease (PD) compared to non‐PD controls, and to assess their impact on motor signs through cross‐sectional and longitudinal analyses. Methods A total of 50 PD participants and 47 age‐ and gender‐matched controls were enrolled. All PD participants were followed up for at least 2 years. To detect regions of greater WMH in the PD, the WMH volume of each region was compared with the corresponding region in the control group. Linear regression and linear mixed effects models were respectively used for cross‐sectional and longitudinal analyses of the impact of increases in WMH volume on motor signs. Results The PD group had greater WMH volume in the occipital region compared with the control group. Cross‐sectional analyses only detected a significant correlation between occipital WMH volume and motor function in PD. Occipital WMH volume positively correlated with the severity of tremor, and gait and posture impairments, in the PD group. During the follow‐up period, the participants' motor signs progressed and the WMH volumes remained stable, no longitudinal association was detected between them. The baseline occipital WMH volume cannot predict the progression of signs after adjustment for baseline disease duration and the presence of vascular risk factors. Interpretation PD participants in this study were characterized by greater WMH at the occipital region, and greater occipital WMH volume had cross‐sectional associations with worse motor signs, while its longitudinal impact on motor signs progression was limited.

Aiming at the problem of high line loss caused by the access station of distributed generation (DG), a two-stage coordinated line loss reduction model based on elephant herding optimization (EHO) and second-order cone programming (SOCP) was put forward by using static var generators (SVG) and energy storage system (ESS) to reduce the line loss from reactive and active power aspects, respectively. Firstly, based on the elephant herding optimization, the location model of distributed generation, SVG and ESS was constructed and determined. On this basis, a cooperative line loss reduction model is proposed, which takes into account multiple line loss reduction methods, such as SVG reactive power compensation device and energy storage. By properly dealing with power flow constraints of distributed generation, the influence of operation control mode of distributed generation on optimal distribution and line loss reduction is precisely explained. The constraint is transformed into a second-order cone programming problem by using second-order cone relaxation. In this way, the coordinated reduction of line loss is realized, and the goal of line loss minimization and voltage stability maximization is achieved. Finally, a practical station is taken as an example to verify the correctness of the proposed model and algorithm and the effectiveness of the proposed method.

Understanding the reproductive characteristics of a species is of crucial for accurate stock assessment and management plans to ensure sustainable fisheries. In this study, the size at 50% sexual maturity (L50) parameters in different bio-ecological provinces were estimated for bigeye tuna, Thunnus obesus, sampled from the Eastern Pacific Ocean tuna fisheries-dependent survey from 2013 to 2019. The overall sex ratio of the catch during the sampling differed significantly from 1:1. Bigeye tuna exhibit sexual dimorphism in the growth of males and females, with a clear shift in predominance from female to male with increasing sizes. In the North Pacific Sub-tropical Gyre (east) (NPST-east), North Pacific Tropical Gyre (NPTG), Pacific North Equatorial Countercurrent (PNEC), and Pacific Equatorial Divergence (PEQD), females (meals) reached sexual maturity round 102 cm (106 cm), 106 cm (100 cm), 125 cm (110 cm), and 113 cm (110 cm), respectively, the estimated L50 of bigeye tuna was 124.08 cm, 121.97 cm, 139.92 cm and 132.45 cm, respectively. The degree of populations mixing between equatorial (PNEC and PEQD) and high-latitude regions (NPST-east and NPTG) is extremely small, but it is reasonably high between the NPST-east and NPTG or PNEC and PEQD. These parameters were significantly different, suggesting the occurrence of a spatial difference in the size-at-maturity of bigeye tuna between these bio-ecological provinces. The findings of this study provide the key information for understanding the life history of bigeye tuna in the Eastern Pacific Ocean and will contribute to the conservation and sustainable yield of this species.

Temperature affects the growth and development of tobacco. With the frequent occurrence of extreme high and low temperature disasters, temperature stress has become one of the important factors restricting the normal growth and physiological functions of flue-cured tobacco. Low temperature stress and high temperature stress are currently the most common disasters in the seedling and maturity stages of flue-cured tobacco, which have a serious impact on the quality and yield of flue-cured tobacco. This article reviews the effects of temperature stress on physiological mechanisms such as growth and development, photosynthetic function, carbon and nitrogen metabolism, and antioxidant system of flue-cured tobacco. It introduced the research progress of related plant proteins and molecular mechanisms in temperature stress, and systematically summarizes the current stress resistance control measures for field temperature stress, including field management and spraying exogenous substances. At present, most agronomic interventions for temperature stress management may not be complete. It is necessary to understand the genetic, biochemical and physiological processes of different varieties in order to identify and select traits, enhance their high-temperature resistance mechanism, and cultivate high-temperature resistant flue-cured tobacco varieties. Looking forward to future research on temperature stress in flue-cured tobacco, including exploring local germplasm resources, cultivating heat-resistant varieties, utilizing methods such as multi omics or cross omics to deeply explore the response mechanism of temperature stress in flue-cured tobacco, developing predictive research on temperature stress in flue-cured tobacco, and developing targeted management measures for stress resistance cultivation, in order to provide scientific support for the prevention of climate disasters and the enhancement of agricultural disaster reduction efficiency for flue-cured tobacco.

Abstract Small extracellular vesicles (sEVs) have been identified as a noteworthy paracrine mechanism of intercellular communication in diagnosing and managing neurological disorders. Current research suggests that sEVs play a pivotal role in the pathological progression of pain, emphasizing their critical function in the pathological progression of pain in acute and chronic pain models. By facilitating the transfer of diverse molecules, such as proteins, nucleic acids, and metabolites, sEVs can modulate pain signaling transmission in both the central and peripheral nervous systems. Furthermore, the unique molecules conveyed by sEVs in pain disorders indicate their potential as diagnostic biomarkers. The application of sEVs derived from mesenchymal stem cells (MSCs) in regenerative pain medicine has emerged as a promising strategy for pain management. Moreover, modified sEVs have garnered considerable attention in the investigation of pathological processes and therapeutic interventions. This review presents a comprehensive overview of the current knowledge regarding the involvement of sEVs in pain pathogenesis and treatment. Nevertheless, additional research is imperative to facilitate their clinical implementation. Graphical Abstract Schematic diagram of sEVs in the biogenesis, signal transmission, diagnosis, and treatment of pain disorders. Small extracellular vesicles (sEVs) are secreted by multiple cells, loading with various biomolecules, such as miRNAs, transmembrane proteins, and amino acids. They selectively target other cells and regulating pain signal transmission. The composition of sEVs can serve as valuable biomarkers for pain diagnosis. In particular, mesenchymal stem cell-derived sEVs have shown promise as regenerative medicine for managing multiple pain disorders. Furthermore, by modifying the structure or contents of sEVs, they could potentially be used as a potent analgesic method.

Abstract Background Diabetes mellitus is a prevalent metabolic disease in the world. Previous studies have shown that anesthetics can affect perioperative blood glucose levels which related to adverse clinical outcomes. Few studies have explored the choice of general anesthetic protocol on perioperative glucose metabolism in diabetes patients. We aimed to compare total intravenous anesthesia (TIVA) with total inhalation anesthesia (TIHA) on blood glucose level and complications in type 2 diabetic patients undergoing general surgery. Methods In this double-blind controlled trial, 116 type 2 diabetic patients scheduled for general surgery were randomly assigned to either the TIVA group or TIHA group (n = 56 and n = 60, respectively). The blood glucose level at different time points were measured and analyzed by the repeated-measures analysis of variance. The serum insulin and cortisol levels were measured and analyzed with t-test. The incidence of complications was followed up and analyzed with chi-square test or Fisher’s exact test as appropriate. The risk factors for complications were analyzed using the logistic stepwise regression. Results The blood glucose levels were higher in TIHA group than that in TIVA group at the time points of extubation, 1 and 2 h after the operation, 1 and 2 days after the operation, and were significantly higher at 1 day after the operation (10.4 ± 2.8 vs. 8.1 ± 2.1 mmol/L; P

Abstract Background The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Methods We conducted a systematic review and meta-analysis to aggregate the clinical outcomes of patients with LM from EGFR-mutant NSCLC treated with osimertinib. A comprehensive literature search for published and unpublished studies was implemented in April 2021 of PubMed, EMBASE, the Cochrane Library, and several international conference databases, in accordance with the PRISMA guidelines. Meta-analysis of proportions was conducted to calculate the pooled rate of overall response rate (ORR), disease control rate (DCR), one-year overall survival (OS), and adverse events (AEs). Results A total of eleven studies (five prospective and six retrospective) including 353 patients were included. The majority of patients (346/353, 98.0%) received osimertinib as ≥ 2nd-line treatment for LM, either at a dosage of 80 mg (161/353, 45.6%) or 160 mg (191/353, 54.1%). The pooled rates of ORR and DCR were 42% (95% CI 24% to 59%) and 93% (95% CI 88% to 97%), respectively. The pooled one-year OS rate was 59% (95% CI 53% to 65%) in 233 patients from five studies. The highest incidence of AEs of all grades was rash (53%), followed by diarrhea (45%), paronychia (35%), decreased appetite (35%), and dry skin (27%), based on data from four studies. Conclusions Our study highlighted and confirmed the meaningful efficacy and a manageable safety profile of osimertinib for the treatment of LM from EGFR-mutant advanced NSCLC.