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Abstract Background MicroRNAs (miRNAs) are critical regulators of cancer progression, prompting our investigation into the specific function of miR-630 in pancreatic cancer stem cells (PCSCs). Analysis of miRNA and mRNA expression data in PCSCs revealed downregulation of miR-630 and upregulation of PRKCI, implying a potential role for miR-630 in PCSC function and tumorigenicity. Results Functional assays confirmed that miR-630 directly targets PRKCI, leading to the suppression of the Hedgehog signaling pathway and consequent inhibition of PCSC self-renewal and tumorigenicity in murine models. This study unveiled the modulation of the PRKCI-Hedgehog signaling axis by miR-630, highlighting its promising therapeutic potential for pancreatic cancer (PC) treatment. Conclusions MiR-630 emerges as a pivotal regulator in PCSC biology, opening up new avenues for targeted interventions in PC. The inhibitory effect of miR-630 on PCSC behavior underscores its potential as a valuable therapeutic target, offering insights into innovative treatment strategies for this challenging disease.

Abstract Background Dysphagia, a common complication of acute stroke, is associated with increased mortality and morbidity. Acupuncture, a widely used swallowing therapy in China, has been suggested as an effective therapy for treating Post-Stroke Dysphagia (PSD) by recent meta-analyses and guidelines. The use of resting-state functional Magnetic Resonance Imaging (rs-fMRI) and Diffusion Tensor Imaging (DTI) could explore the change of regional spontaneous neural activity, functional relationships between brain regions, and white matter connectivity patterns after acupuncture intervention for PSD. This trial aims to evaluate the efficacy of acupuncture treatment for PSD and explore its central mechanism by neuroimaging. Methods/design This randomized controlled trial will recruit 40 PSD patients. All patients will be randomized to either the Real Acupuncture (RA) or Sham Acupuncture (SA) group by a ratio of 1:1. All patients will receive immediate acupuncture treatment in the MRI scanning room, followed by four weeks of long-term acupuncture treatment. The primary outcomes are the rs-fMRI and DTI indicators, which will be evaluated after the immediate and long-term acupuncture treatment. The secondary outcomes are the scales that assess the efficacy, including the Functional Oral Intake Scale (FOIS), Water Swallowing Test (WST), Swallowing Quality Of Life Questionnaire (SWAL-QOL), and National Institute of Health Stroke Scale (NIHSS). The modified version of the Massachusetts General Hospital Acupuncture Sensation Scale (M-MASS) and fMRI sensation record table will also be evaluated. Discussion This protocol presents the design of a randomized, single-blind trial that will evaluate the efficacy and explore the neural plasticity of acupuncture treatment for PSD. This trial will deepen our insight into the clinical value of acupuncture for PSD and initially probe into the time-dosage-effect mechanism of acupuncture. Trial registration numbers Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2300067480. This study was registered on 9th January 2023.

In order to solve the problem of rancidity of rice polishing powder and improve its physicochemical properties, the effects of twin-screw extrusion under different extrusion temperatures on the storage stability and nutritional properties of rice polishing powder were studied. Under the optimum extrusion temperature, the rice polishing powder (SR-1, SR-2, SR-3, and SR-4) with different particle sizes was prepared by low temperature impact mill (LTIM) under different air classifier speeds (300, 600, 1200, and 1800 r/min). The effects of the air classifier speed on volatile aroma compounds and physicochemical properties of rice polishing powder were studied. The results showed that the lipase activity of rice polishing powder decreased significantly from 12.94 mg/g to 2.18 mg/g after extrusion treatment. Stored at the 150th day, the fatty acid value of untreated rice polishing powder was 255.57 mg KOH/100 g, while the fatty acid value of the extruded sample was only 121.90 mg KOH/100 g. After extrusion treatment, dietary fiber, γ-aminobutyric acid, and γ-oryzanol in rice polishing powder were also well retained. LTIM promoted the release of volatile aroma compounds in rice polishing powder, and SR-3 had the highest concentration. Based on the partial least square discriminant, 9 differentially labeled components were screened according to the importance projection of variables, and it was confirmed that SR-3 had the strongest flavor. With the decrease of particle size, the specific surface area of rice polishing powder gradually increased, and the bulk density showed a decreasing trend. The whiteness index increased significantly from 66.08 to 76.61. Water absorption ability and solubility increased significantly from 1.77 g/g and 24% to 2.37 g/g and 31%, respectively. Fourier transform infrared spectroscopy analysis showed that LTIM destroyed hydrogen bonds in starch particles, resulting in more free hydroxyl group exposure. The results can provide a theoretical basis and technical support for the processing of high-quality rice polishing powder.

Abstract Cognitive dysfunction caused by diabetes has become a serious global medical issue. Diabetic kidney disease (DKD) exacerbates cognitive dysfunction in patients, although the precise mechanism behind this remains unclear. Here, we conducted an investigation using RNA sequencing data from the Gene Expression Omnibus (GEO) database. We analyzed the differentially expressed genes in DKD and three types of neurons in the temporal cortex (TC) of diabetic patients with cognitive dysfunction. Through our analysis, we identified a total of 133 differentially expressed genes (DEGs) shared between DKD and TC neurons (62 up-regulated and 71 down-regulated). To identify potential common biomarkers, we employed machine learning algorithms (LASSO and SVM-RFE) and Venn diagram analysis. Ultimately, we identified 8 overlapping marker genes (ZNF564, VPS11, YPEL4, VWA5B1, A2ML1, KRT6A, SEC14L1P1, SH3RF1) as potential biomarkers, which exhibited high sensitivity and specificity in ROC curve analysis. Functional analysis using Gene Ontology (GO) revealed that these genes were primarily enriched in autophagy, ubiquitin/ubiquitin-like protein ligase activity, MAP-kinase scaffold activity, and syntaxin binding. Further enrichment analysis using Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) indicates that these biomarkers may play a crucial role in the development of cognitive dysfunction and diabetic nephropathy. Building upon these biomarkers, we developed a diagnostic model with a reliable predictive ability for DKD complicated by cognitive dysfunction. To validate the 8 biomarkers, we conducted RT-PCR analysis in the cortex, hippocampus and kidney of animal models. The results demonstrated the up-regulation of SH3RF1 in the cortex, hippocampus and kidney of mice, which was further confirmed by immunofluorescence and Western blot validation. Notably, SH3RF1 is a scaffold protein involved in cell survival in the JNK signaling pathway. Based on these findings, we support that SH3RF1 may be a common gene expression feature that influences DKD and cognitive dysfunction through the apoptotic pathway.

Abstract Background The effectiveness and safety of acupuncture therapy to delay lung function decline in chronic obstructive pulmonary disease (COPD) remain unclear. This study aimed to determine whether acupuncture, as an adjunctive therapy to COPD-guided medication, could prevent lung function decline. Methods This randomised, two-centre study was conducted between February 2022 and July 2023. Men and women aged 40–80 years with COPD were recruited. Participants received active or sham acupuncture three times a week (36 sessions total). The primary outcome was the change in the percentage of forced expiratory volume for 1 s to the predicted value (FEV1%) between the baseline and after the intervention. Results Overall, 238 participants were screened, and 74 (58 men [78.4%]; mean [standard deviation] age, 69.6 [7.2] years) were randomised into the acupuncture and sham acupuncture groups (37 per group). After the intervention, the change in FEV1% was 1.35 (95% confidence interval [CI]: -0.47 to 3.17) and -2.44 (95% CI: -4.56 to -0.33) in the acupuncture and sham acupuncture groups, respectively. The difference was -3.97 (95% CI: -6.2 to -1.74), and the adjusted difference was -3.46 (95% CI: -5.69 to -1.24, P = 0.003) between the groups. A significantly less decline was found in forced expiratory volume for 1 s in the acupuncture group. All treatment-related adverse events (acupuncture = 11, sham = 2) were mild. Conclusions Compared with sham acupuncture, acupuncture plus medication may delay lung function decline. However, further studies with a larger sample size and longer-term follow-up are needed to clarify the effects.

Arbuscular mycorrhizae (AM) fungi form symbiotic associations with plant roots, providing nutritional benefits and promoting plant growth and defenses against various stresses. Metabolic changes in the roots during AM fungal colonization are key to understanding the development and maintenance of these symbioses. Here, we investigated metabolic changes in the roots of peanut (Arachis hypogaea L.) plants during the colonization and development of AM symbiosis, and compared them to uncolonized roots. The primary changes during the initial stage of AM colonization were in the contents and compositions of phenylpropanoid and flavonoid compounds. These compounds function in signaling pathways that regulate recognition, interactions, and pre-colonization between roots and AM fungi. Flavonoid compounds decreased by 25% when the symbiosis was fully established compared to the initial colonization stage. After AM symbiosis was established, general metabolism strongly shifted toward the formation of lipids, amino acids, carboxylic acids, and carbohydrates. Lipid compounds increased by 8.5% from the pre-symbiotic stage to well-established symbiosis. Lyso-phosphatidylcholines, which are signaling compounds, were only present in AM roots, and decreased in content after the symbiosis was established. In the initial stage of AM establishment, the content of salicylic acid increased two-fold, whereas jasmonic acid and abscisic acid decreased compared to uncolonized roots. The jasmonic acid content decreased in roots after the symbiosis was well established. AM symbiosis was associated with high levels of calcium, magnesium, and D-(+)-mannose, which stimulated seedling growth. Overall, specific metabolites that favor the establishment of AM symbiosis were common in the roots, primarily during early colonization, whereas general metabolism was strongly altered when AM symbiosis was well-established. In conclusion, specialized metabolites function as signaling compounds to establish AM symbiosis. These compounds are no longer produced after the symbiosis between the roots and AM becomes fully established.

Abstract Parameter identification of solar photovoltaic (PV) cells is crucial for the PV system modeling. However, finding optimal parameters of PV models is an intractable problem due to the highly nonlinear characteristics between currents and voltages in different environments. To address this problem, whale optimization algorithm (WOA)-based meta-heuristic algorithm has turned out to be a feasible and effective approach. As a highly promising optimization algorithm, different enhanced WOA variants have been proposed. Nevertheless, there has been no comparative study of WOA and its variants for parameter identification of PV models so far. To further investigate and analyze the performance of WOA in the studied problem, this work applied and compared WOA and ten enhanced WOA variants for identifying five PV model parameters. Different evaluation indices including solution accuracy, search robustness, and convergence curve were employed to reveal their performance variation. Based on the simulation results, a multi-model statistical analysis with the Friedman test at a confidence level 0.05 was conducted to rank all algorithms. EWOA that hybridizes the sorting-based differential mutation operator and the Lévy flight strategy ranked first and its performance was further verified. Besides, according to the simulation results, possible effective improvement directions for WOA in tackling this intractable problem are concluded to guide future work.

PurposeThis study aimed to investigate the impact of coexisting metabolic dysfunction-associated steatotic liver disease (MASLD) on in-hospital mortality and organ injury markers in patients with heat stroke (HS).ApproachHS patients were retrospectively identified between July 1, 2022 and September 30, 2023 at West China Hospital, Sichuan University. Baseline characteristics, such as demographics, initial vital signs, and organ functional indicators were collected. Outcome events included organ injury and in-hospital mortality. The Least Absolute Shrinkage and Selection Operator (Lasso) method was employed to identify the optimal predictors for in-hospital mortality in HS patients. Subsequently, multivariable logistic regression analysis was performed to assess the relationship between the presence of MASLD and in-hospital mortality as well as organ function indicators.FindingsA total of 112 patients were included in the study, in which 27 (24.1%) had coexisting MASLD. Compared to those without MASLD, patients with MASLD had higher levels of various organ injury markers such as aspartate aminotransferase, urea nitrogen, serum cystatin C, creatinine, uric acid, myoglobin, creatine kinase and its isoenzymes upon admission (P < 0.05). The multivariable Logistic regression analysis indicated that the presence of MASLD is an independent risk factor for in-hospital mortality in HS patients.ConclusionThis study firstly indicated that coexisting MASLD may exacerbate organ injury in HS patients and serve as an independent risk factor for in-hospital mortality.

Better soil structure promotes extension of plant roots thereby improving plant growth and yield. Differences in soil structure can be determined by changes in the three phases of soil, which in turn affect soil function and fertility levels. To compare the quality of soil structure under different conditions, we used Generalized Soil Structure Index (GSSI) as an indicator to determine the relationship between the “input” of soil three phases and the “output” of soil structure. To achieve optimum monitoring of comprehensive indicators, we used Successive Projections Algorithm (SPA) for differential processing based on 0.0–2.0 fractional orders and 3.0–10.0 integer orders and select important wavelengths to process soil spectral data. In addition, we also applied multivariate regression learning models including Gaussian Process Regression (GPR) and Artificial Neural Network (ANN), exploring potential capabilities of hyperspectral in predicting GSSI. The results showed that spectral reflection, mainly contributed by long-wave near-infrared radiation had an inverse relationship with GSSI values. The wavelengths between 404-418 nm and 2193–2400 nm were important GSSI wavelengths in fractional differential spectroscopy data, while those ranging from 543 to 999 nm were important GSSI wavelengths in integer differential spectroscopy data. Also, non-linear models were more accurate than linear models. In addition, wide neural networks were best suited for establishing fractional-order differentiation and second-order differentiation models, while fine Gaussian support vector machines were best suited for establishing first-order differentiation models. In terms of preprocessing, a differential order of 0.9 was found as the best choice. From the results, we propose that when constructing optimal prediction models, it is necessary to consider indicators, differential orders, and model adaptability. Above all, this study provided a new method for an in-depth analyses of generalized soil structure. This also fills the gap limiting the detection of soil three phases structural characteristics and their dynamic changes and provides a technical references for quantitative and rapid evaluation of soil structure, function, and quality.

Abstract Background Sepsis-associated encephalopathy (SAE) causes acute and long-term cognitive deficits. However, information on the prevention and treatment of cognitive dysfunction after sepsis is limited. The neuropeptide orexin-A (OXA) has been shown to play a protective role against neurological diseases by modulating the inflammatory response through the activation of OXR1 and OXR2 receptors. However, the role of OXA in mediating the neuroprotective effects of SAE has not yet been reported. Methods A mouse model of SAE was induced using cecal ligation perforation (CLP) and treated via intranasal administration of exogenous OXA after surgery. Mouse survival, in addition to cognitive and anxiety behaviors, were assessed. Changes in neurons, cerebral edema, blood-brain barrier (BBB) permeability, and brain ultrastructure were monitored. Levels of pro-inflammatory factors (IL-1β, TNF-α) and microglial activation were also measured. The underlying molecular mechanisms were investigated by proteomics analysis and western blotting. Results Intranasal OXA treatment reduced mortality, ameliorated cognitive and emotional deficits, and attenuated cerebral edema, BBB disruption, and ultrastructural brain damage in mice. In addition, OXA significantly reduced the expression of the pro-inflammatory factors IL-1β and TNF-α, and inhibited microglial activation. In addition, OXA downregulated the expression of the Rras and RAS proteins, and reduced the phosphorylation of P-38 and JNK, thus inhibiting activation of the MAPK pathway. JNJ-10,397,049 (an OXR2 blocker) reversed the effect of OXA, whereas SB-334,867 (an OXR1 blocker) did not. Conclusion This study demonstrated that the intranasal administration of moderate amounts of OXA protects the BBB and inhibits the activation of the OXR2/RAS/MAPK pathway to attenuate the outcome of SAE, suggesting that OXA may be a promising therapeutic approach for the management of SAE.

Alzheimer′s disease (AD) is a neurodegenerative disease with extremely complex pathogenesis, characterized by cognitive dysfunction and memory loss, involving in a variety of physiological and pathophysiological processes. Early diagnosis is a key factor for the prevention and treatment of AD. Positron emission tomography (PET) technology can accurately detect subtle physiological changes in neurons and brain tissues at the molecular level, providing evidence for early diagnosis of AD. Starting from the classification of biomarkers, the relevant targets of protein degeneration and neuronal damage in the brain were introduced, and the research status of various PET tracers was reviewed according to several important parameters such as affinity, half-life, binding region, pharmacokinetics, analysis method and correlation of results, etc. Additionally, the current problems faced by the development of PET tracers were pointed out, and it was believed that future research should be carried out from the following aspects: The development of PET tracers related to neuroinflammation; Further evaluation and optimization of existing tracers; Normalization and standardization of methods for the analysis of tracer results.

Abstract Hexavalent chromium (Cr(VI)) is still a common contaminant in water. In this work, we studied the Cr(VI) adsorption by polyphenol-rich bacterial cellulose(BC) gel, synthesized by the Komagataeibacter rhaeticus K15 using wine pomace. The results showed that the equilibrium removal capacity was 473.09 ± 1.41 mg g−1 (dry weight). The quasi-second-order kinetics model and the Langmuir removal isotherm model was the most suitable for describing the Cr(VI) removal process. Toxic Cr(VI) was converted to the low toxic Cr(III) during the removal process via the reduction of Cr(VI) to Cr(III) by polyphenols released into the solution by the BC gel. The FTIR, XRD, XPS, SEM-EDX results indicated the physical adsorption on the surface of BC and the reduction reaction between polyphenol groups and Cr(VI) is the critical mechanism of Cr(VI) removal by BC. The finding of this study demonstrates that polyphenols-rich BC gel produced from wine pomace has a superior feature for future Cr(VI)-wastewater purification.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose–effect relationship of acupuncture. Methods/design This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. Discussion This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. Trial registration This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

Condyloma latum is a typical lesion of secondary syphilis，which usually appears in the vicinity of the initial chancre. It is found that treponema pallidum load in condyloma latum is significantly higher than that in other secondary syphilis. We report a case of mesosyphilis presented as giant flat condyloma latum in vulvar and perianal areas. A 17-year female patient came to our clinic，complaining of plaques in vulvar and perianal areas more than 2 months. Physical examination showed giant red moist plaques in vulvar and perianal areas. The titer of non-specific antibody for syphilis was 1∶64 and the specific antibody test for syphilis showed a value of 189.000 COI. The patient was diagnosed as secondary syphilis and treate with benzathine penicillin. The rash subsided after 3-week treatment. This case of condyloma latum with giant red plaques was easily misdiagnosed as condyloma acuminatum.

Abstract Background Gut microbiota alterations have been implicated in sepsis and related infectious diseases, but the causal relationship and underlying mechanisms remain unclear. Methods We evaluated the association between gut microbiota composition and sepsis using two-sample Mendelian randomization (MR) analysis based on published genome-wide association study (GWAS) summary statistics. Sensitivity analyses were conducted to validate the robustness of the results. Reverse MR analysis and integration of GWAS and expression quantitative trait loci (eQTL) data were performed to identify potential genes and therapeutic targets. Results Our analysis identified 11 causal bacterial taxa associated with sepsis, with increased abundance of six taxa showing positive causal relationships. Ten taxa had causal effects on the 28-day survival outcome of septic patients, with increased abundance of six taxa showing positive associations. Sensitivity analyses confirmed the robustness of these associations. Reverse MR analysis did not provide evidence of reverse causality. Integration of GWAS and eQTL data revealed 76 genes passing the summary data-based Mendelian randomization (SMR) test. Differential expression of these genes was observed between sepsis patients and healthy individuals. These genes represent potential therapeutic targets for sepsis. Molecular docking analysis predicted potential drug-target interactions, further supporting their therapeutic potential. Conclusion Our study provides insights for the development of personalized treatment strategies for sepsis and offers preliminary candidate targets and drugs for future drug development.

Abstract This study aimed to develop and validate a predictive model to determine the risk of in-hospital mortality in patients with acute paraquat poisoning. This retrospective observational cohort study included 724 patients with acute paraquat poisoning whose clinical data were collected within 24 h of admission. The primary outcome was in-hospital mortality. Patients were randomly divided into training and validation cohorts (7/3 ratio). In the training cohort, the least absolute shrinkage and selection operator regression models were used for data dimension reduction and feature selection. Multivariate logistic regression was used to generate a predictive nomogram for in-hospital mortality. The prediction model was assessed for both the training and validation cohorts. In the training cohort, decreased level of consciousness (Glasgow Coma Scale score

The significant demand for high quality food has motivated us to adopt appropriate processing methods to improve the food nutritional quality and flavors. In this study, the effects of five drying methods, namely, pulsed vacuum drying (PVD), freeze drying (FD), infrared drying (IRD), hot-air drying (HAD) and sun drying (SD) on free amino acids (FAAs), α-dicarbonyl compounds (α-DCs) and volatile compounds (VOCs) in rape bee pollen (RBP) were determined. The results showed that FD significantly released the essential amino acids (EAAs) compared with fresh samples while SD caused the highest loss. Glucosone was the dominant α-DCs in RBP and the highest loss was observed after PVD. Aldehydes were the dominant volatiles of RBP and SD samples contained more new volatile substances (especially aldehydes) than the other four drying methods. Comprehensively, FD and PVD would be potential methods to effectively reduce the quality deterioration of RBP in the drying process.

Ischemic stroke is a devastating condition that occurs due to the interruption of blood flow to the brain, resulting in a range of cellular and molecular changes. In recent years, there has been growing interest in the role of ferroptosis, a newly identified form of regulated cell death, in ischemic stroke. Ferroptosis is driven by the accumulation of lipid peroxides and is characterized by the loss of membrane integrity. Additionally, oxidative stress, which refers to an imbalance between prooxidants and antioxidants, is a hallmark of ischemic stroke and significantly contributes to the pathogenesis of the disease. In this review, we explore the interactions between ferroptosis and oxidative stress in ischemic stroke. We examine the underlying mechanisms through which oxidative stress induces ferroptosis and how ferroptosis, in turn, exacerbates oxidative stress. Furthermore, we discuss potential therapeutic strategies that target both ferroptosis and oxidative stress in the treatment of ischemic stroke. Overall, this review highlights the complex interplay between ferroptosis and oxidative stress in ischemic stroke and underscores the need for further research to identify novel therapeutic targets for this condition.

Objective This study aimed to assess the accuracy of Mac-2 binding protein glycosylation isomer (M2BPGi) in predicting the stage of liver fibrosis. Methods Articles published until October 10, 2023, were searched in the PubMed, Embase, Web of Science, and Cochrane Library databases. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), summary receiver–operator curves (SROC), and Spearman’s rank correlation coefficient were used to examine the accuracy of M2BPGi in predicting the stage of liver fibrosis. A 95% confidence interval (CI) was provided for each estimate. Results Twenty-four studies were included in this meta-analysis, including 3,839 patients with liver fibrosis, 409 of whom progressed to stage 4 or above. The pooled sensitivity, specificity, and area under the ROC (AUC) for M2BPGi predicting liver fibrosis ≥F3 were 0.74 (95% CI [0.65–0.82]), 0.84 (95% CI [0.76–0.89]), and 14.99 (95% CI [9.28–24.21]), respectively. The pooled sensitivity, specificity, and AUC for ≥F4 were 0.80 (95% CI [0.70–0.88]), 0.80 (95% CI [0.73–0.86]), and 16.43 (95% CI [0.84–0.90]), respectively. Conclusion Among different sample partitions, M2BPGi has the best diagnostic performance for liver fibrosis stage ≥4. Furthermore, the cutoff of 1–2 is more accurate than that of 0–1 or 2–3 for fibrosis ≥ F3 and ≥ F4. Registration CRD42023483260.

Electroacupuncture pretreatment is considered as an optimal strategy for inducing cerebral ischaemic tolerance. However, the underlying neuroprotective mechanism of this approach has never been explored from the perspective of calcium homeostasis. Intracellular calcium overload is a key inducer of cascade neuronal injury in the early stage after cerebral ischaemia attack and the Na+/Ca2+ exchanger (NCX) is the main plasma membrane calcium extrusion pathway maintaining post-ischaemic calcium homeostasis. This study aims to investigate whether the regulation of NCX-mediated calcium transport contributes to the cerebroprotective effect of electroacupuncture pretreatment against ischaemic injury and to elucidate the underlying mechanisms involved in this process. Following five days of repeated electroacupuncture stimulation on Baihui (GV20), Neiguan (PC6), and Sanyinjiao (SP6) acupoints in rats, in vivo and in vitro models of cerebral ischaemia were induced through middle cerebral artery occlusion and oxygen/glucose deprivation (OGD), respectively. Firstly, we verified the neuroprotective effect of electroacupuncture pretreatment from the perspective of neurological score, infarct volume and neuronal apoptosis. Our findings from brain slice patch-clamp indicated that electroacupuncture pretreatment enhanced the Ca2+ efflux capacity of NCX after OGD. NCX1 expression in the ischaemic penumbra exhibited a consistent decline from 1 to 24 h in MCAO rats. Electroacupuncture pretreatment upregulated the expression of NCX1, especially at 24 h, and silencing NCX1 by short hairpin RNA (shRNA) administration reversed the protective effect of electroacupuncture pretreatment against cerebral ischaemic injury. Furthermore, we administered LY294002, a phosphatidylinositol 3 kinase (PI3K) inhibitor, prior to inducing ischaemia to investigate the upstream regulatory mechanism of electroacupuncture pretreatment on NCX1 expression. Electroacupuncture pretreatment activates PI3K/Akt pathway, leading to an increase in the expression of NCX1, which facilitates calcium extrusion and exerts a neuroprotective effect against cerebral ischaemia. These findings provided a novel insight into the prevention of ischemic stroke and other similar conditions characterized by brain ischaemia or hypoperfusion.

Background: This study aims to explore the microtubule-associated gene signatures and molecular processes shared by osteonecrosis of the femoral head (ONFH) and osteosarcoma (OS). Methods: Datasets from the TARGET and GEO databases were subjected to bioinformatics analysis, including the functional enrichment analysis of genes shared by ONFH and OS. Prognostic genes were identified using univariate and multivariate Cox regression analyses to develop a risk score model for predicting overall survival and immune characteristics. Furthermore, LASSO and SVM-RFE algorithms identified biomarkers for ONFH, which were validated in OS. Function prediction, ceRNA network analysis, and gene–drug interaction network construction were subsequently conducted. Biomarker expression was then validated on clinical samples by using qPCR. Results: A total of 14 microtubule-associated disease genes were detected in ONFH and OS. Subsequently, risk score model based on four genes was then created, revealing that patients with low-risk exhibited superior survival outcomes compared with those with high-risk. Notably, ONFH with low-risk profiles may manifest an antitumor immune microenvironment. Moreover, by utilizing LASSO and SVM-RFE algorithms, four diagnostic biomarkers were pinpointed, enabling effective discrimination between patients with ONFH and healthy individuals as well as between OS and normal tissues. Additionally, 21 drugs targeting these biomarkers were predicted, and a comprehensive ceRNA network comprising four mRNAs, 71 miRNAs, and 98 lncRNAs was established. The validation of biomarker expression in clinical samples through qPCR affirmed consistency with the results of bioinformatics analysis. Conclusion: Microtubule-associated genes may play pivotal roles in OS and ONFH. Additionally, a prognostic model was constructed, and four genes were identified as potential biomarkers and therapeutic targets for both diseases.

Abstract Tumor‐derived exosomes are crucial for early non‐invasive and accurate tumor diagnosis in clinical diagnostics. The development of highly sensitive, simple, and intuitive exosome assays has sparked a research upsurge in clinical diagnostics. Here, we develop a bio‐responsive intelligent DNA hydrogel loaded with CRISPR/Cas12a for universal and ultrasensitive detection of the exosomes. The aptamer serves as the target response unit and switch, competitively disintegrating the region of the DNA linkers and then Cas12a/crRNA was released and activated, resulting in a high fluorescent intensity for exosome detection at the detection limit of 119 particles/μL. Moreover, a constructed colorimetric tube is made by loading a colorimetric filter membrane on the tube lid and intelligent DNA hydrogel on the tube bottom, which enables one‐pot portable colorimetric detection. Without the need for laboratory instruments and professionals, this strategy allows for naked eye detection with limit of detection as low as 104 particles/μL, and shows great applicability in distinguishing between healthy individuals, pretreatment patients, and post‐treatment patients after obtaining a testable analyte. In this study, an ultrasensitive detection platform for exosomes that enables one‐step sensing and dual signal output was introduced. The findings here suggest that this platform is a promising tool for the application of liquid biopsy based on exosomes in clinical diagnosis.

BackgroundThe efficacy and safety of different immunosuppressants combined with chemotherapy in treating patients with small-cell lung cancer (extensive-disease small-cell lung cancer, limited-disease small-cell lung cancer and relapsed small-cell lung cancer) are still unknown, and there are no reports directly comparing the efficacy and safety of other immunotherapies.ObjectiveThis study aimed to compare the efficacy and safety of first-line immunotherapy combined with chemotherapy in patients with small-cell lung cancer.MethodWe searched Pubmed, Embase, Cochrane Library, CNKI, and Wanfang databases for relevant articles published from inception to November 11, 2020. The risk of bias of the included studies was conducted using the Cochrane risk-of-bias (RoB) tool. Multiple Bayesian network meta-analyses were performed. They conducted data analysis using R Studio and STATA version 15.1. The outcomes comprised overall survival (OS), progression-free survival (PFS), stability of response (SOR), duration of response (DOR) and adverse events of grade 3 or higher (AE grade≥3). A 95% confidence interval (CI) was provided for each estimate.ResultsThis meta-analysis included 16 RCT studies with 5898 patients. For OS, relative to chemotherapy (MD=-4.49; 95%CI [-7.97, -1.03]), durvalumab plus tremelimumab (MD=-4.62; 95%CI [-9.08, -0.11]), ipilimumab (MD=-4.26; 95%CI [-8.01, -0.3]) and nivolumab(MD=-5.66; 95%CI [-10.44, -1.11]) and nivolumab plus ipilimumab (MD=-4.56; 95%CI [-8.7, -0.1]), serplulimab can significantly increase the OS of SCLC patients. There was no significant difference between PFS, SOR and DOR. Analysis of AE showed that different immunotherapy combined chemotherapy regimens were similar to single chemotherapy regarding the overall incidence of AE grade≥3. However, after the cumulative ranking of the common symptoms of different adverse reactions, it was found that nivolumab ranked first in the occurrence probability of anemia (99.08%), fatigue (84.78%), and decreased appetite (89.66%). durvalumab was the most likely in nausea (75.4%). Pembrolizumab (76.24%) was most likely to cause pruritus. Chemotherapy combined with immunotherapy caused less diarrhea than chemotherapy alone (80.16%).ConclusionsAccording to our analysis, serplulimab combined with chemotherapy is more likely to show better efficacy with a manageable safety profile for small-cell lung cancer. However, the evidence for this comparison shows some limitations due to the number of literature.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023486053.

Resistance to targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) is a significant challenge in the treatment of this disease. The mechanisms of resistance are multifactorial and include molecular target alterations and activation of alternative pathways, tumor heterogeneity and tumor microenvironment change, immune evasion, and immunosuppression. Promising strategies for overcoming resistance include the development of combination therapies, understanding the resistance mechanisms to better use novel drug targets, the identification of biomarkers, the modulation of the tumor microenvironment and so on. Ongoing research into the mechanisms of resistance and the development of new therapeutic approaches hold great promise for improving outcomes for patients with NSCLC. Here, we summarize diverse mechanisms driving resistance to targeted therapy and immunotherapy in NSCLC and the latest potential and promising strategies to overcome the resistance to help patients who suffer from NSCLC.

Summary: In glioma molecular subtyping, existing biomarkers are limited, prompting the development of new ones. We present a multicenter study-derived consensus immune-related and prognostic gene signature (CIPS) using an optimal risk score model and 101 algorithms. CIPS, an independent risk factor, showed stable and powerful predictive performance for overall and progression-free survival, surpassing traditional clinical variables. The risk score correlated significantly with the immune microenvironment, indicating potential sensitivity to immunotherapy. High-risk groups exhibited distinct chemotherapy drug sensitivity. Seven signature genes, including IGFBP2 and TNFRSF12A, were validated by qRT-PCR, with higher expression in tumors and prognostic relevance. TNFRSF12A, upregulated in GBM, demonstrated inhibitory effects on glioma cell proliferation, migration, and invasion. CIPS emerges as a robust tool for enhancing individual glioma patient outcomes, while IGFBP2 and TNFRSF12A pose as promising tumor markers and therapeutic targets.

Abstract Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core “S-D-A-D-S” NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application. Graphical Abstract

Abstract Developing versatile, scalable, and durable coatings that resist the accretion of matters (liquid, vapor, and solid phases) in various operating environments is important to industrial applications, yet has proven challenging. Here, we report a cellular coating that imparts liquid-repellence, vapor-imperviousness, and solid-shedding capabilities without the need for complicated structures and fabrication processes. The key lies in designing basic cells consisting of rigid microshells and releasable nanoseeds, which together serve as a rigid shield and a bridge that chemically bonds with matrix and substrate. The durability and strong resistance to accretion of different matters of our cellular coating are evidenced by strong anti-abrasion, enhanced anti-corrosion against saltwater over 1000 h, and maintaining dry in complicated phase change conditions. The cells can be impregnated into diverse matrixes for facile mass production through scalable spraying. Our strategy provides a generic design blueprint for engineering ultra-durable coatings for a wide range of applications.

Abstract Pepper (Capsicum spp.) is one of the earliest cultivated crops and includes five domesticated species, C. annuum var. annuum, C. chinense, C. frutescens, C. baccatum var. pendulum and C. pubescens. Here, we report a pepper graph pan-genome and a genome variation map of 500 accessions from the five domesticated Capsicum species and close wild relatives. We identify highly differentiated genomic regions among the domesticated peppers that underlie their natural variations in flowering time, characteristic flavors, and unique resistances to biotic and abiotic stresses. Domestication sweeps detected in C. annuum var. annuum and C. baccatum var. pendulum are mostly different, and the common domestication traits, including fruit size, shape and pungency, are achieved mainly through the selection of distinct genomic regions between these two cultivated species. Introgressions from C. baccatum into C. chinense and C. frutescens are detected, including those providing genetic sources for various biotic and abiotic stress tolerances.

Abstract Without coordinated strategies to balance the population and activity of tumor cells and polarized macrophages, antitumor immunotherapy generally offers limited clinical benefits. Inspired by the “eat me” signal, a smart tumor cell‐derived proximity anchored non‐linear hybridization chain reaction (Panel‐HCR) strategy is established for on‐demand regulation of tumor‐associated macrophages (TAMs). The Panel‐HCR is composed of a recognition‐then‐assembly module and a release‐then‐regulation module. Upon recognizing tumor cells, a DNA nano‐tree is assembled on the tumor cell surface and byproduct strands loaded with CpG oligodeoxynucleotides (CpG‐ODNs) are released depending on the tumor cell concentration. The on‐demand release of CpG‐ODNs can achieve efficient regulation of M2 TAMs into the M1 phenotype. Throughout the recognition‐then‐assembly process, tumor cell‐targeted bioimaging is implemented in single cells, fixed tissues, and living mice. Afterward, the on‐demand release of CpG‐ODNs regulate the transformation of M2 TAMs into the M1 phenotype by stimulating toll‐like receptor 9 to activate the NF‐κB pathway and increasing inflammatory cytokines. This release‐then‐regulation process is verified to induce strong antitumor immune responses both in vitro and in vivo. Altogether, this proposed strategy holds tremendous promise for on‐demand antitumor immunotherapy.

BackgroundEarly-onset sarcopenia refers to the progressive loss of muscle mass and function that occurs at an early age. This condition perpetuates the vicious cycle of muscle loss and is associated with adverse outcomes. It is important to identify the contributing factors for early intervention and prevention. While diet is known to impact muscle mass, the association of B vitamins with early-onset sarcopenia remains unexplored.ObjectivesTo investigate the association of B vitamins intake with early-onset sarcopenia risk in a cross-sectional study.MethodsWe conducted data analysis on a total of 8,711 participants aged between 20 and 59 years who took part in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Early-onset sarcopenia was defined as a SMI measured by DXA that was one standard deviation below the sex-specific mean of the reference population. B vitamins intake (B1, B2, B3, B6, B9, and B12) was assessed by 24-h dietary recall. We used weighted multiple logistic regression and RCS models to estimate the OR and 95% CI of sarcopenia by B vitamins intake, adjusting for demographic, physical, lifestyle, comorbidities, and nutritional covariates.ResultsHigher intake of vitamin B1 was associated with a 22% lower sarcopenia risk (OR = 0.78, CI = 0.63–0.97, p = 0.022), and higher intake of vitamin B2 with a 16% lower risk (OR = 0.84, CI = 0.74–0.97, p = 0.012) in both genders. Gender-specific analyses showed a 28% reduction in sarcopenia risk among males with each additional mg of vitamin B1 intake (OR = 0.72, CI = 0.52–0.97, p = 0.038), and a 26% decrease among females with each additional mg of vitamin B2 intake (OR = 0.74, CI = 0.57–0.96, p = 0.021). No significant differences were found between vitamin B2 and males, or between vitamin B1 and females. The RCS model suggested a nonlinear relationship between vitamin B2 intake and sarcopenia risk (POverall = 0.001, PNonlinear = 0.033), with a plateau effect above 3 mg/d.ConclusionHigher intake of vitamin B1 and B2 may lower the risk of early-onset sarcopenia, with gender differences. This suggests the potential of nutritional intervention by increasing these vitamins intake through diet and supplements. Further research is warranted to elucidate the mechanisms and design targeted interventions.

Background During active infections, plants prevent further spread of pathogenic microorganisms by inducing the rapid programmed death of cells around the infection point. This phenomenon is called the hypersensitive response and is a common feature of plant immune responses. Plants recognize conserved structures of pathogenic microorganisms, called pathogen-associated molecular patterns (PAMPs), e.g., flagellin 22 (flg22) and chitohexose, which bind to receptors on plant cells to induce various immune-response pathways. Although abiotic stresses are known to alter photosynthesis, the different effects of flg22 and chitohexose, which are involved into PAMP-induced signaling, on photosynthesis needs further study. Methods In the present study, we assessed the role of PAMPs in peanut (Arachis hypogaea) photosynthesis, particularly, the interaction between PAMPs and Ca2+ signal transduction pathway. Results Both flg22 and chitohexose significantly promoted the expression of the pathogenesis-related genes PR-4 and PR-10, as did Ca2+. We found that Ca2+ is involved in downregulating the photosystem II (PSII) reaction center activity induced by the flg22 immune response, but the role of chitohexose is not obvious. Additionally, Ca2+ significantly reduced the non-photochemical energy dissipation in the flg22- and chitohexose-induced immune response. Conclusion These results indicated that flg22 and chitohexose can trigger peanut immune pathways through the Ca2+ signaling pathway, but they differ in their regulation of the activity of the PSII reaction center.

Whether receptor activity-modifying proteins (RAMPs) play a key role in human cancer prognosis and immunity remains unknown. We used data from the public databases, The Cancer Genome Atlas, Therapeutically Applicable Research to Generate Effective Treatments, and the Genotype-Tissue Expression project. We utilized bioinformatics methods, R software, and a variety of online databases to analyze RAMPs. In general, RAMPs were significantly and differentially expressed in multiple tumors, and RAMP expression was closely associated with prognosis, immune checkpoints, RNA-editing genes, tumor mutational burden, microsatellite instability, ploidy, and stemness indices. In addition, the expression of RAMPs is strongly correlated with tumor-infiltrating lymphocytes in human cancers. Moreover, the RAMP co-expression network is largely involved in many immune-related biological processes. Quantitative reverse transcription polymerase chain reaction and Western blot proved that RAMP3 was highly expressed in glioma, and RAMP3 promoted tumor proliferation and migration. RAMPs exhibit potential as prognostic and immune-related biomarkers in human cancers. Moreover, RAMPs can be potentially developed as therapeutic targets or used to enhance the efficacy of immunotherapy.

IntroductionRecently, moral distress in pediatric nursing has gained academic attention, yet comprehensive literature reviews on this group are scarce.AimsThis study aims to offer a detailed overview of moral distress among pediatric nurses, focusing on understanding its characteristics, prevalence, underlying causes, and consequences on the quality of patient care.MethodsEmploying a scoping review approach as recommended by the Joanna Briggs Institute, this study will systematically search through PubMed, Scopus, Web of Science, APA PsycInfo, and CINAHL databases using specific search strategies. Titles, abstracts, and full texts will be independently screened by two reviewers according to the eligibility criteria. Relevant data will be extracted, categorized, and subjected to narrative synthesis to draw comprehensive insights.ConclusionThe anticipated findings of this study will shed light on the nature, frequency, and drivers of moral distress among pediatric nurses, along with its broader implications for healthcare practitioners, organizational practices, and patient care outcomes.

Background. Liver injury related to heatstroke plays a pivotal role in secondary multiorgan damage and is a direct cause of mortality in affected patients of heatstroke. This study was designed to identify independent risk factors associated with liver injury in heatstroke and to construct a clinically applicable predictive model. Methods. We conducted a retrospective analysis of 188 patients diagnosed with heatstroke, treated in the emergency departments of eight medical institutions from July 1, 2022, to September 30, 2023. Patients were categorized into a liver injury group (n = 80) and a nonliver injury group (n = 108), based on liver function indices recorded during hospitalization. Lasso regression was employed for variable refinement, while multifactorial logistic regression was utilized to identify independent risk factors for liver injury in heatstroke and to construct a nomogram model. The model’s efficacy was evaluated using the C-index, calibration curves, and decision curve analysis, examining its discriminative ability, calibration, and clinical utility. Results. The nomogram included predictive factors such as the Glasgow score, absolute lymphocyte count, lactate dehydrogenase levels, and creatine kinase isoenzyme. The model showed high accuracy and discriminative capability. The C-index was 0.852 (95% CI 0.80–0.905) with a calibration index of 0.843. Decision curve analysis revealed significant clinical applicability for this nomogram. Conclusion. The study identified four key independent risk factors for liver injury in heatstroke patients. The constructed nomogram, based on the four clinical indicators, demonstrated robust predictive accuracy, discriminative power, and clinical relevance.

This study aims to identify key factors and sensitive intervals affect the school road traffic characteristics. We collect traffic data from the parking area and the school road (400-700 meters). The simulation is calibrated to ensure the error of outputs are within 1.5%. A sensitivity analysis method is proposed, it makes the multifactor comparable. The sensitivity factors of vehicle delay, queue length, and average speed are 1.44, 2.03, and 0.28 in school road, and the bottleneck road are 3.07, 4.44, and 0.65. The traffic indicators change more concentrated in bottleneck road but greater in school road. 6 scenarios are created to analyze school road traffic characteristics. Traffic flow (TF), number of parking spaces (NPS), and stopping time (ST) are selected as variables. Scenarios 1-3 are univariate, and scenarios 4-6 are bivariate. TF is the key factor with a sensitivity interval of [1300,1700].

Abstract Background The amyloid probability score (APS) is the model read‐out of the analytically validated mass spectrometry‐based PrecivityAD® blood test that incorporates the plasma Aβ42/40 ratio, ApoE proteotype, and age to identify the likelihood of brain amyloid plaques among cognitively impaired individuals being evaluated for Alzheimer's disease. Purpose This study aimed to provide additional independent evidence that the pre‐established APS algorithm, along with its cutoff values, discriminates between amyloid positive and negative individuals. Methods The diagnostic performance of the PrecivityAD test was analyzed in a cohort of 200 nonrandomly selected Australian Imaging, Biomarker & Lifestyle Flagship Study of Aging (AIBL) study participants, who were either cognitively impaired or healthy controls, and for whom a blood sample and amyloid PET imaging were available. Results In a subset of the dataset aligned with the Intended Use population (patients aged 60 and older with CDR ≥0.5), the pre‐established APS algorithm predicted amyloid PET with a sensitivity of 84.9% (CI: 72.9–92.1%) and specificity of 96% (CI: 80.5–99.3%), exclusive of 13 individuals for whom the test was inconclusive. Interpretation The study shows individuals with a high APS are more likely than those with a low APS to have abnormal amounts of amyloid plaques and be on an amyloid accumulation trajectory, a dynamic and evolving process characteristic of progressive AD pathology. Exploratory data suggest APS retains its diagnostic performance in healthy individuals, supporting further screening studies in the cognitively unimpaired.

The stay-green trait is of considerable importance in extending the shelf life of green pepper fruit (Capsicum annuum L.) and in enhancing the appearance of ornamental plants. The study revealed the genetic and regulatory mechanisms of the stay-green trait in pepper, which will aid in the selection of ornamental pepper varieties. In this study, a pepper mutant with stay-green fruit named TNX348 was identified from a germplasm resource bank. Two segregating populations were constructed using the stay-green mutant TNX348 and then used in bulked segregant analysis combined with RNA sequencing and linkage analyses. The causal gene of the stay-green trait was mapped to an approximately 131-kb region, and a senescence-induced chloroplast protein gene, CaSGR1 (Capana01g000359), was identified as a candidate gene. Sequencing analysis revealed a G→A single-base mutation of CaSGR1 in TNX348 that led to early termination of translation. Based on the single-base mutation, a single nucleotide polymorphism (SNP) marker co-segregating with the stay-green trait was developed. Furthermore, in transcriptome analysis, expression patterns of 11 hormone transduction-related transcription factors, such as abscisic acid-insensitive (ABI), abscisic acid-responsive element-binding factor (ABF), and NAC transcription factor, were similar or opposite to that of CaSGR1. The results indicated that the transcription factors might mediate chlorophyll degradation by regulating the expression of CaSGR1.

In rice cultivation and breeding, obtaining accurate information on the quantity and spatial distribution of rice plants is crucial. However, traditional field sampling methods can only provide rough estimates of the plant count and fail to capture precise plant locations. To address these problems, this paper proposes P2PNet-EFF for the counting and localization of rice plants. Firstly, through the introduction of the enhanced feature fusion (EFF), the model improves its ability to integrate deep semantic information while preserving shallow spatial details. This allows the model to holistically analyze the morphology of plants rather than focusing solely on their central points, substantially reducing errors caused by leaf overlap. Secondly, by integrating efficient multi-scale attention (EMA) into the backbone, the model enhances its feature extraction capabilities and suppresses interference from similar backgrounds. Finally, to evaluate the effectiveness of the P2PNet-EFF method, we introduce the URCAL dataset for rice counting and localization, gathered using UAV. This dataset consists of 365 high-resolution images and 173,352 point annotations. Experimental results on the URCAL demonstrate that the proposed method achieves a 34.87% reduction in MAE and a 28.19% reduction in RMSE compared to the original P2PNet while increasing R2 by 3.03%. Furthermore, we conducted extensive experiments on three frequently used plant counting datasets. The results demonstrate the excellent performance of the proposed method.

Abstract Tumor microenvironment (TME)‐triggered phototheranostic platform offers a feasible strategy to improve cancer diagnosis accuracy and minimize treatment side effects. Developing a stable and biocompatible molecular phototheranostic platform for TME‐activated second near‐infrared (NIR‐II) fluorescence imaging‐guided multimodal cascade therapy is a promising strategy for creating desirable anticancer agents. Herein, a new NIR‐II fluorescence imaging‐guided activatable molecular phototheranostic platform (IR‐FEP‐RGD‐S‐S‐S‐Fc) is presented for actively targeted tumor imaging and hydrogen sulfide (H2S) gas‐enhanced chemodynamic‐hypothermal photothermal combined therapy (CDT/HPTT). It is revealed for the first time that the coupling distance between IR‐FE and ferrocene is proportional to the photoinduced electron transfer (PET), and the aqueous environment is favorable for PET generation. The part of Cyclic‐RGDfK (cRGDfk) peptides can target the tumor and benefit the endocytosis of nanoparticles. The high‐concentration glutathione (GSH) in the TME will separate the fluorescence molecule and ferrocene by the GSH‐sensitive trisulfide bond, realizing light‐up NIR‐II fluorescence imaging and a cascade of trimodal synergistic CDT/HPTT/gas therapy (GT). In addition, the accumulation of hydroxyl radicals (•OH) and down‐regulation of glutathione peroxidase 4 (GPX4) can produce excessive harmful lipid hydroperoxides, ultimately leading to ferroptosis.

The increasing warming and humidification have caused the dramatic degradation of Qinghai-Tibet Plateau permafrost. The active layer thickness (ALT) is particularly crucial to be monitored with a wide range as an indispensable variable to characterize permafrost status. Interferometric synthetic aperture radar (InSAR) technology has recently been widely used for ALT retrieval. However, these studies are mostly limited by the accuracy of one-dimensional deformation measurements and ignore the presence of unfrozen water in the negative temperature state of the soil. Therefore, an improved ALT retrieval model using InSAR technology is proposed considering the influence of two-dimensional deformation and unfrozen water. This paper first employed the multidimensional small baseline subset (MSBAS) technology to monitor two-dimensional surface deformation over the Beiluhe-Wudaoliang permafrost region. We observed that the study area underwent surface subsidence of up to 60 mm in the thawing season. Considering the influence of unfrozen water, the ALT was subsequently estimated using the InSAR-observed subsidence. The estimated ALT varied from 50 to 500 cm, with ALT in the Wudaoliang area being higher than that in the Beiluhe Basin. Based on in situ data, the improved method is better than the traditional InSAR-based methods with a mean absolute error of 0.404 m. Our study demonstrates that considering the influence of two-dimensional deformation and unfrozen water can effectively improve the accuracy and reliability of InSAR-based ALT retrieval.

Background: The utilization of acupuncture as a therapeutic intervention for the management of postoperative nausea and vomiting has experienced a notable increase in its popularity, and the purpose of this analysis is to provide a comprehensive understanding of the level of concern within the academic discipline and the main contributors and their partnership, as well as to identify research focal points and trends. Methods: A comprehensive search was carried out to identify relevant articles on the topic of acupuncture therapy for PONV in the Web of Science and China National Knowledge Internet. The search spanned from January 1, 2011, to June 6, 2023. The annual publications were count to see the degree of scholarly attention devoted to the discipline and how it has changed over time. A statistical analysis of article distribution across various journals was conducted to serve a rough indicator for assessing the quality of articles. And a bibliometric analysis was conducted using the software CiteSpace to visually analyze various aspects of the literature. Analyze authors, institutions and countries to identify the main contributors and their collaborative relationship; and analyze keywords and references to explore research hotspots and trends. Results: This study examined a comprehensive collection of 819 articles focused on acupuncture therapy for PONV, demonstrating a varying upward trend in the quantity of publications. Notably, the most productive author and institution were identified as Zheng Man and Guangzhou University of Traditional Chinese Medicine, respectively. While China had the highest number of publications, the United States held a greater prominence in this specific field. Collaboration among contributors was found to be weak. High-frequency keywords in the publications included ''transcutaneous electrical acupoint stimulation,'' ''electroacupuncture,'' ''pain,'' and so forth. The literature with the highest citation count pertained to “Stimulation of the wrist acupuncture point PC6 for preventing postoperative nausea and vomiting,” while the article with the highest centrality was “Consensus Guidelines for the Management of Postoperative Nausea and Vomiting.” Several large clusters obtained from the references are also included “postoperative pain,” “transcutaneous electrical acupoint stimulation”. Nothing pertaining to mechanism study was found in the analysis results. Conclusion: The utilization of acupuncture for the treatment of postoperative nausea and vomiting has been gaining increasing recognition, although there remains room for improvement in the quality of research conducted in this area. Chinese authors and institutions have emerged as significant contributors to this field, while the United States has demonstrated greater proficiency in fostering collaborative efforts. It is imperative to enhance collaboration among these contributors. The current focal points of acupuncture for PONV encompass pain management, electroacupuncture, auricular acupuncture, and transcutaneous electrical acupoint stimulation. Additionally, TEA and enhanced recovery after surgery have been identified as the forefronts of research in this particular domain. In addition, there is still much room for research in the aspect of mechanism and insurance coverage. This study provides an in-depth perspective on acupuncture for PONV, which offers reference material for clinicians with rational choice of therapeutic scheme, educators with hot topics, and researchers with valuable research directions.

BackgroundThe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common respiratory disease among older adults, which imposes a significant burden on individuals and society and poses a major challenge to the global public health system due to its high morbidity and mortality. Acupuncture is effective for AECOPD, but its efficacy has been questioned due to the limited methodological quality. Thus, we aim to investigate the efficacy of acupuncture as adjunctive therapy for AECOPD and determine whether the efficacy of acupuncture differs with the type of acupoint combinations.Methods and analysisThis study proposes a prospective, multicenter randomized controlled trial that will comprise four groups, including two acupuncture treatment groups, one sham acupuncture group, and one basic treatment group. The acupuncture treatment groups will be distinguished by their focus on different patterns of acupoint combination, namely the Xi-cleft and He-sea acupoint combination and the Eight Confluence points acupoint combination, which may vary in clinical efficacy based on traditional acupuncture theories. The study aims to randomize 556 patients in a 1:1:1:1 ratio across the four groups. Each patient in acupuncture group or sham acupuncture group will receive routine drug therapy and 7 sessions of acupuncture treatment over 1 week. Participants in the basic treatment group will only receive routine drug therapy. The trial will be conducted in seven hospitals located in China. The primary outcomes in this trial will include differences in the Breathlessness, Cough, and Sputum Scale (BCSS) before randomization, 7 days after randomization, 5 and 9 weeks after randomization.Ethics and disseminationEthical approval was obtained from the Sichuan Regional Ethics Review of Committee on Traditional Chinese Medicine (Approval ID: 2022KL-068). The results of this study will be distributed through peer-reviewed journals.Clinical Trial Registration: ClinicalTrials.gov, identifier ChiCTR2200064484.