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Abstract Forests are invaluable natural resources that provide essential services to humanity. However, the effects of global warming on forest carbon and nitrogen cycling remain uncertain. Here we project a decrease in total nitrogen input and accumulation by 7 ± 2 and 28 ± 9 million tonnes (Tg), respectively, and an increase in reactive nitrogen losses to the environment by 9 ± 3 Tg for 2100 due to warming in a fossil-fueled society. This would compromise the global carbon sink capacity by 0.45 ± 0.14 billion tonnes annually. Furthermore, warming-induced inequality in forest carbon and nitrogen cycles could widen the economic gap between the Global South and Global North. High-income countries are estimated to gain US$179 billion in benefits from forest assets under warming, while other regions could face net damages of US$31 billion. Implementing climate-smart forest management, such as comprehensive restoration and optimizing tree species composition, is imperative in the face of future climate change.

Objective To study the effectiveness and safety of ultrasound-guided pectoral nerve block combined with no background patient controlled intravenous analgesia (PCIA) in postoperative pain control of partial mastectomy patients. Methods A total of 60 patients who underwent elective partial mastectomy at Pukou Traditional Chinese Medicine Hospital Affiliated to China Pharmaceutical University from May 2022 to May 2023 were selected and divided into group M and group N, with 30 cases in each growp. Both groups received no background PCIA. Patients in M group received 0.2% ropivacaine 30 mL for pectoral nerve block, while patients in group N did not receive any other treatment. The outcome measures were VAS scores during static and coughing at the time point of patient leaving resuscitation room (T0), 4 hours (T1), 12 hours (T2), 24 hours (T3), and 48 hours (T4) after surgery, as well as the total analgesia consumption and rescue analgesia dosage. Results Patients in group M showed a lower rest VAS at T0, T1, T2, and T3 time point (P＜0.05), and lower cough VAS at T0, T1, and T2 time point than patients in group N (P＜0.05). In group M, the total intravenous analgesia consumption and number of presses were significantly less than group N at 48 hours after surgery (P＜0.05). There was no statistically significant difference in the incidence of postoperative adverse reactions between the two groups (P＞0.05), and there was no complication related to nerve block in group M. Conclusion Ultrasound-guided pectoral nerve block combined with no background PCIA is able to provide potent postoperative pain control, reduce analgesia consumption in partial mastectomy patients.

Mounting evidence strongly indicates that exosomes are pivotal in the advancement of cancer, yet the overarching profile of exosomal proteins and their contribution to lung adenocarcinoma (LUAD) progression remain underexplored. In our investigation, we isolated exosomes from treatment-naive LUAD (n = 20) and paired normal adjacent tissues (NATs), and conducted integrated proteomic on the acquired exosomes and source tissues to ascertain origin characteristics and potential therapeutic targets of the exosomal proteins in LUAD. The omics data revealed the overall landscape of exosomal proteins from tissues in LUAD, underscoring the profound linkage between exosomal proteins and tumor metastasis. Integrated analysis indicated a significant overlap in protein species, demonstrating high concordance between exosomal proteins and those in their originating tissues. However, only a small subset showed significant positive correlation in protein abundance between exosomes and their source tissues. Notably, we pinpointed five proteins (DDX18, DNAJA3, PAFAH1B3, BAG6, and CAD). Significantly, platelet activating factor acetylhydrolase 1b catalytic subunit 3 (PAFAH1B3), an essential serine hydrolase within cellular metabolic processes, stood out as the singular protein closely associated with disease-free survival (DFS) of patients. Cell invasion and migration assays further substantiated that PAFAH1B3 promoted metastasis of LUAD via the exosomal release pathway. Furthermore, analysis of public databases validated elevated PAFAH1B3 expression in LUAD and linked it to poor patient survival outcomes. Overall, our research positioned PAFAH1B3 as a promising candidate for prognostic marker and potential therapeutic target in lung cancer treatment.

IntroductionThe utilization of denosumab in treating osteoporosis highlights promising prospects for osteoporosis intervention guided by gene targets. While omics-based research into osteoporosis pathogenesis yields a plethora of potential gene targets for clinical transformation, identifying effective gene targets has posed challenges.MethodsWe first queried the omics data of osteoporosis clinical samples on PubMed, used International Mouse Phenotyping Consortium (IMPC) to screen differentially expressed genes, and conducted preliminary functional verification of candidate genes in human Saos2 cells through osteogenic differentiation and mineralization experiments. We then selected the candidate genes with the most significant effects on osteogenic differentiation and further verified the osteogenic differentiation and mineralization functions in mouse 3T3-E1 and bone marrow mesenchymal stem cells (BMSC). Finally, we used RNA-seq to explore the regulation of osteogenesis by the target gene.ResultsWe identified PPP2R2A, RRBP1, HSPB6, SLC22A15, ADAMTS4, ATP8B1, CTNNB1, ROBO1, and EFR3B, which may contribute to osteoporosis. ROBO1 was the most significant regulator of osteogenesis in both human and mouse osteoblast. The inhibitory effect of Robo1 knockdown on osteogenic differentiation may be related to the activation of inflammatory signaling pathways.ConclusionOur study provides several novel molecular mechanisms involved in the pathogenesis of osteoporosis. ROBO1 is a potential target for osteoporosis intervention.

Abstract The association between cooking fuel and hearing loss still needs more research to clarify, and two longitudinal cohort studies were explored to find if solid fuel use for cooking affected hearing in Chinese adults. The data from Chinese Health and Retirement Longitudinal Survey (CHARLS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Participants (older than 18) without hearing loss at baseline and follow-up visits were included, which were divided into clean fuel and solid fuel groups. Hearing loss rate was from follow-up visits (both in year 2011) until the recent one (year 2018 in CHARLS and 2019 in CLHLS). Cox regressions were applied to examine the associations with adjustment for potential confounders. Fixed-effect meta-analysis was used to pool the results. A total of 9049 participants (average age 8.34 ± 9.12 [mean ± SD] years; 4247 [46.93%] males) were included in CHARLS cohort study and 2265 participants (average age, 78.75 ± 9.23 [mean ± SD] years; 1148 [49.32%] males) in CLHLS cohort study. There were 1518 (16.78%) participants in CHARLS cohort and 451 (19.91%) participants in CLHLS cohort who developed hearing loss. The group of using solid fuel for cooking had a higher risk of hearing loss (CHARLS: HR, 1.16; 95% CI 1.03–1.30; CLHLS: HR, 1.43; 95% CI 1.11–1.84) compared with the one of using clean fuel. Pooled hazard ratio showed the incidence of hearing loss in the solid fuel users was 1.17 (1.03, 1.29) times higher than that of clean fuel users. Hearing loss was associated with solid fuel use and older people were at higher risk. It is advised to replace solid fuel by clean fuel that may promote health equity.

ObjectiveTo establish variation trajectories and reference values of body mass index (BMI) for 0 – 6 year old children in Yanbian Korean Autonomous Prefecture (Yanbian) using the lambda-mu-sigma (LMS) method, and to analyze disparities between the BMI of local children and those of national references to evaluate the growth and development of children in the Yanbian region. MethodsUsing stratified random cluster sampling, we collected data from 6 650 children aged 0 – 6 years (1 557/1 860 and 1 356/1 859 Korean/Han boys and girls) who received a physical examination at five community health centers in five counties/prefectures in Yanbian region in September 2019. Simultaneous modeling of mean (mu), coefficient of variation (sigma), and skewness (lambda) of the children′s BMI was performed using the LMS method to calculate percentiles 3, 25, 50, 75, 97 of age-specific reference BMI values.ResultsVariations in BMI showed a similar trend with age among the boys and girls surveyed. There were significant gender differences in age-specific BMI values, with boys having higher mean BMIs than girls at 3 months (17.43 ± 1.53 vs. 16.77 ± 1.48), 6 months (17.89 ± 1.73 vs. 17.35 ± 1.62), 1 year (17.10 ± 1.44 vs. 16.72 ± 1.32), 1.5 years (16.53 ± 1.31 vs. 15.94 ± 1.26), 2 years (16.46 ± 1. 45 vs. 16.10 ± 1.50), 2.5 years (16.26 ± 1.32 vs. 15.73 ± 1.44), 3.5 years (16.11 ± 1.62 vs. 15.66 ± 1.69), 4.5 years (15.80 ± 1.74 vs. 15.51 ± 1. 70), 5 years (16.03 ± 2.10 vs. 15.54 ± 1.83), 5.5 years (16.44 ± 2.55 vs. 15.69 ± 1.86), and 6 years (16.77 ± 2.88 vs. 16.07 ± 2.76), respectively (all P < 0.05). The participants′ BMI growth trajectories derived from the LMS analysis showed that for the surveyed boys between one month and one year of age and girls between one month and 1.5 years of age, all percentile values of age-specific BMI were lower than those of the national reference values; but for the surveyed boys older than one year of age and girls older than 1.5 years of age, all the percentile values of age-specific BMI of were higher than those of the national reference values, except for the percentile 3 values, which were lower than those of the national reference values. ConclusionFor the children aged 0 – 6 years in Yanbian region, the BMI values of boys are generally higher than those of girls and the overall BMI values of the children have exceeded the national reference values.

Alien species are colonizing mountain ecosystems and increasing their elevation ranges in response to ongoing climate change and anthropogenic disturbances, posing increasing threats to native species. However, how quickly alien species spread upward and what drives their invasion remains insufficiently understood. Here, using 26,952 occurrence records of 58 alien plant species collected over two centuries in the Czech Republic, we explored the elevation range and invasion speed of each alien species and the underlying factors driving these variables. We collected species traits relevant for invasion (e.g., clonality, flowering time, life span, invasion status, height, mycorrhizal type, native range, naturalized range, monoploid genome size, and Ellenberg-type indicator values for light, temperature, and nitrogen), human-associated factors (e.g., introduction pathways and the sum of economic use types), and minimum residence time. We explored the relationships between these factors and species’ elevation range and invasion speed using phylogenetic regressions. Our results showed that 58 alien species have been expanding upward along mountain elevations in the Czech Republic over the past two centuries. A stronger effect of species’ traits than human-associated factors has been revealed, e.g., clonality was a key trait supporting the invasion of alien species into the mountains, while human-associated factors showed no effect. Our findings highlight that the characteristics associated with rapid reproduction and spread are crucial for alien species’ invasion into montane regions. Identifying key drivers of this process is important for predicting the spatiotemporal dynamics of alien species in high-altitude ecosystems and thus employing apposite measures to reduce the threat to native plant species.

The tolerance of Saccharomyces cerevisiae to high concentrations of bile acids is intricately linked to its potential as a probiotic. While the survival of yeast under high concentrations of bile acids has been demonstrated, the specific mechanisms of tolerance remain inadequately elucidated. This study aims to elucidate the tolerance mechanisms of S. cerevisiae CEN.PK2-1C under conditions of elevated bile acid concentrations. Through growth curve analyses and scanning electron microscopy (SEM), we examined the impact of high bile acid concentrations on yeast growth and cellular morphology. Additionally, transcriptomic sequencing and molecular docking analyses were employed to explore differentially expressed genes under high bile acid conditions, with particular emphasis on ATP-binding cassette (ABC) transporters and steroid hormone biosynthesis. Our findings indicate that high concentrations of bile acids induce significant alterations in the sterol synthesis pathway and transporter protein expression in S. cerevisiae. These alterations primarily function to regulate sterol synthesis pathways to maintain cellular structure and sustain growth, while enhanced expression of transport proteins improves tolerance to elevated bile acid levels. This study elucidates the tolerance mechanisms of S. cerevisiae under high bile acid conditions and provides a theoretical foundation for optimizing fermentation processes and process control.

Abstract Background Alzheimer’s disease (AD) is the most prevalent neurodegenerative and remains incurable. Aluminum is a potent neurotoxin associated with AD. The main pathological features of AD are extracellular amyloid-β protein deposition and intracellular hyperphosphorylated Tau protein. A body of evidence suggest that oxidative stress and autophagy are involved in the pathogenesis of AD. Andrographis paniculata (AP) is a native plant with anti-inflammatory, anti-oxidative stress, and regulation of autophagy properties. AP significantly alleviated cognitive impairments, reduced Aβ deposition and has neuroprotective effect. However, its effects on aluminum-induced AD model have not been studied much. In this study, we investigated whether AP protect against aluminum-induced neurotoxicity through regulation of p62-Kelch-like ECH-associated protein 1(Keap1)-Nuclear factor E2 related factor 2 (Nrf2) pathway and activation autophagy in vivo and in vitro. Methods UPLC-ESI-qTOF-MS/MS was used to identify the chemical constituents of AP ethanol extract. The mice with cognitive deficit were established by injecting aluminum chloride and D-galactose, and treated with either AP extract (200, 400, or 600 mg/kg/d) or andrographolide (2 mg/kg/2d).The spatial memory ability was detected by Morris water maze, HE staining were used to detect in brain tissue,Oxidative stress indexs and SOD activity in both serum and brain tissue were detected by kit.The expression of p62-Nrf2 pathway proteins were measured via western blotting. Furthermore, the neurotoxicity model was induced by aluminum maltolate (700 µM) in PC12 cells. Following AP and andrographolide treatment, the cell viability was detected. The relevant mRNA and protein expressions were detected in cells transfected with the p62 siRNA. Results The main active components of AP included andrographolide, neoandrographolide and deoxyandrographolide as identified. AP and andrographolide significantly improved the spatial memory ability of mice, attenuated pathological changes of hippocampal cells, reduced the level of malondialdehyde, and increased superoxide dismutase activity in serum or brain tissue as compared to model control. In addition, the Nrf2, p62 and LC3B-II proteins expression were increased, and p-Tau and Keap1 proteins were decreased in the hippocampus after AP and andrographolide treatment.Furthermore, AP increased aluminum maltolate-induced cell viability in PC12 cells. Silencing p62 could reverse the upregulation expression of Nrf2 and downregulation of Keap1 and Tau proteins induced by AP in aluminum maltolate-treated cells. Conclusions AP had neuroprotective effects against aluminum -induced cognitive dysfunction or cytotoxicity, which was involved in the activation of the p62-keap1-Nrf2 pathway and may develop as therapeutic drugs for the treatment of AD. However, this study has certain limitations, further optimize the protocol or model and study the molecular mechanism of AP improving AD.

Abstract Postbiotics have received increasing interest for their storage stability and safety compared to probiotics, as well as their potential functionality. In this study, edible Lactobacillus plantarum J26 postbiotics (J26P) were prepared by spray drying using skimmed milk as the medium, and 1113 compounds were identified. The aim of this study was to evaluate the cholesterol lowering effect of J26P on hypercholesterolemic mice induced by a high‐fat and high‐cholesterol diet (HCD). The results suggest that J26P significantly alleviated weight gain and appetite reduction in HCD mice. J26P also improved serum and liver biochemical parameters at various levels, including lower total cholesterol (TC), triglyceride (TG), low‐density lipoprotein cholesterol (LDL‐C) in the serum, and TC, TG, LDL‐C, glutamic oxaloacetic transaminase, and glutamic‐pyruvic transaminase in the liver, and increase high‐density lipoprotein cholesterol in the serum and liver. Moreover, liver histopathologic examinations revealed that J26P significantly inhibited fat accumulation and degeneration in hypercholesterolemic mice and increased the expression of liver uncoupling protein 1. Furthermore, the J26P intervention effectively promoted the reduction of cholesterol levels in hypercholesterolemic mice via the LXRα‐CYP7A1‐bile acid‐excretion pathway, which was corroborated by the increased fecal total cholesterol and fecal total bile acid levels. This work provided a theoretical basis for the industrial development of postbiotics and the alleviation of hypercholesterolemia and its complications.

Unmanned aerial vehicle （UAV） inspections now have emerged as a predominant approach for the examination of transmission lines， with a pivotal focus on the detection of insulator defects. In this context， a lightweight insulator defect detection algorithm， founded on the improved YOLOv5， is introduced. Firstly， the lightweight Ghost convolution is employed to replace conventional convolution. Subsequently， the original feature extraction network is replaced with a repeated weighted bidirectional feature pyramid network （BiFPN） to bolster feature extraction capability across various scales. Finally， the coordinate attention （CA） mechanism is introduced to enhance the efficiency of backbone feature extraction. Experimental results reveal a significant 1.7% enhancement in the average precision of insulator detection， accompanied by a 13.1% reduction in the model’s size. This refined algorithm model not only elevates detection accuracy but also streamlines its footprint， thereby enabling more efficient and rapid insulator defect detection.

Abstract To compare early diabetic retinopathy (DR) severity level and the abilities in detecting early DR lesions among conventional five-field, ultrawide-field (UWF) Optos, and UWF Clarus fundus imaging methods. This was a single-center, prospective, clinic-based, and comparative study. In total, 157 consecutive patients with diabetes mellitus were enrolled in this study. All patients underwent comprehensive ophthalmological examinations. Following mydriasis, each eye was examined with conventional five-field, UWF Optos, and UWF Clarus fundus imaging methods. The initial UWF images were overlaid with a template mask that obscured the retina, which created a five-field view from UWF images (covered UWF images). The covered UWF images were then graded, after which the template mask was removed, and the original UWF images were also evaluated. All images were graded using the International Clinical DR severity scale. DR grades were compared and analyzed by weighted kappa statistics among the three fundus imaging methods. In total, 157 consecutive patients with diabetes (302 eyes) were enrolled in this study. Weighted kappa statistics for agreement were 0.471 (five-field vs. covered Optos), 0.809 (five-field vs. covered Clarus), 0.396 (covered Optos vs. covered Clarus), 0.463 (five-field vs. Optos), 0.521 (five-field vs. Clarus 133°), 0.500 (five-field vs. Clarus 200°), 0.323 (Optos vs. Clarus 133°), and 0.349 (Optos vs. Clarus 200°). The area under curve of covered Clarus images was higher than that of conventional five-field images at three different thresholds. Compared with conventional five-field and Optos fundus imaging methods, Clarus fundus imaging methods exhibited excellent performance in assessing early DR severity. Thus, Clarus fundus imaging methods were superior for early detection of DR.

Abstract Background Chronic active Epstein-Barr virus infection (CAEBV) is a systemic EBV-positive lymphoproliferative disorder (EBV-LPD) considered to be associated with a genetic immunological abnormality, although its cause is still unclear. EBV is usually detected in T cells or NK cells in CAEBV patients with only a few cases involving B cells described in East Asia, which may be due to differences in genetic and environmental factors. Case description A 16-year-old boy who seemed to be diagnosed as CAEBV of B cell type was studied. The patient had IM-like symptoms persisting for more than 3 months, high levels of EBV DNA in the PB, and positive EBER in situ hybridization in B cells. In addition, to exclude underlying genetic disorders, we performed next-generation sequencing (NGS) and whole-exome sequencing (WES), which identified the missense mutation in PIK3CD (E1021K), ADA (S85L) and CD3D (Q140K) in the patient while no same genetic mutation was detected in his parents and sister. However, there is no diagnosis of CAEBV of B cell type in the most recent World Health Organization classification of tumors of hematopoietic and lymphoid tissues, therefore we finally diagnosed this patient as EBV-B-LPD. Conclusions This study shows a rare case of a patient meeting the definition of CAEBV B-cell disease in East Asia. Meanwhile, the case indicates that the missense mutation and the disease are related.

The objective of this study was to explore the effects of cold atmospheric plasma (CAP) treatment on the biological behavior of human gingival fibroblasts (HGFs) cultured on the surface of high-transparency zirconia. Two types of zirconia, 3Y-ZTP and 4Y-PSZ, were subjected to a CAP treatment for various treatment durations. Analyses of the physical and chemical properties of 3Y-ZTP and 4Y-PSZ were conducted using scanning electron microscopy, contact angle measurements, and X-ray photoelectron spectroscopy, both before and after CAP treatment. The biological responses of HGFs on both surfaces were assessed using CCK-8 assay, confocal laser scanning microscopy, and real-time PCR. Initially, the oxygen and hydroxyl contents on the surface of 4Y-PSZ exceeded those on 3Y-ZTP. CAP treatment enhanced the surface hydrophilicity and the reactive oxygen species (ROS) content of 4Y-PSZ, while not altering the surface morphology. After CAP treatment, HGFs’ adhesion on 4Y-PSZ was superior, with more pronounced effects compared to 3Y-ZTP. Notably, HGFs counts and the expression of adhesion-related genes on 4Y-PSZ peaked following the CAP exposures for 30 s and 60 s. Consequently, this study demonstrates that, following identical CAP treatments, 4Y-PSZ is more effective in promoting HGFs adhesion compared to traditional 3Y-ZTP zirconia.

BackgroundAcute promyelocytic leukemia (APL) with PML/RARα fusion gene is a distinct variant of acute myeloid leukemia. According to the different break sites of the PML gene, there are three transcripts: Long (bcr1), Variant (bcr2) and Short (bcr3).MethodsWe retrospectively analyzed 82 APL cases with PML-RARα short isoform.ResultsA total of 384 patients with APL were seen, of which 85(22.14%) had PML/RARα short isoform (bcr3) and 82 met the inclusion criteria. The median age was 33.5 years (range, 2-72 years). The incidences of hemorrhage in the intermediate- and high-risk group were higher, but only the incidence between medium and low risk differed statistically (P=0.006), and the incidences of fever, fatigue, splenomegaly, and lymph node enlargement and differentiation syndrome (DS) in those groups were not statistically significant (P>0.05). FLT3 gene mutation rate and the mortality rate of the high-risk group were significantly higher than that of other groups (P=0.040 and P=0.004, P=0.041 and P=0.037, respectively). The mortality rate was lowest (4.26%) in the group treated with ATRA combined with arsenic and anthracycline. The 3-year OS and the 3-year DFS of the low and intermediate-risk group were better (P=0.019 and P=0.017, respectively).ConclusionsATRA combined with arsenic and anthracycline had significant impact on outcomes in APL with PML-RARα short isoform.

The pathological features of Alzheimer's disease (AD), a progressive neurodegenerative disorder, include the deposition of extracellular amyloid beta (Aβ) plaques and intracellular tau neurofibrillary tangles. A decline in cognitive ability is related to the accumulation of Aβ in patients with AD. Autophagy, which is a primary intracellular mechanism for degrading aggregated proteins and damaged organelles, plays a crucial role in AD. In this review, we summarize the most recent research progress regarding the process of autophagy and the effect of autophagy on Aβ. We further discuss some typical monomers of natural products that contribute to the clearance of Aβ by autophagy, which can alleviate AD. This provides a new perspective for the application of autophagy modulation in natural product therapy for AD.