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Abstract Deer antlers are the only mammalian appendages that can fully regenerate from periosteum of pedicles (PP). This regeneration process starts from regenerative healing of wounds. Removal of PP abolishes antler regeneration, however, the regenerative cutaneous wound healing proceeds, indicating that some factors in the circulation contribute to this healing. In this study, we produced a wound in the scalp of deer either in antler regeneration period (ARP) (n = 3) or in non-ARP (n = 3). Results showed full regeneration took place only when the wound was created during ARP. Interestingly, topical application of systemic factors from ARP (n = 9) promoted regenerative wound healing in rats. Comparative proteomics analysis (n = 3) revealed that PRG4 and IGF-1 were high during ARP, and topical application of PRG4 + IGF-1 promoted restoration in rat FTE wounds. We believe that, ultimately, incorporating systemic factors into advanced wound care modalities could offer new opportunities for regenerative healing in the clinical setting.

Abstract Background Regeneration is the preferred approach to restore the structure and function after tissue damage. Rapid proliferation of cells over the site of damage is integral to the process of regeneration. However, even subtle mutations in proliferating cells may cause detrimental effects by eliciting abnormal differentiation. Interestingly deer antlers, arguably the fastest regenerating mammalian tissue, have not been reported, thus far, to grow malignant tumors. They provide a mammalian model to understand the possible mechanism by which rapid regeneration is achieved while avoiding the development of malignancies. Antler regeneration is based on the proliferation and differentiation of antler stem cells (AnSCs). Results We identified 39 hub genes which may function in regulating the balance between rapid proliferation and genomic stability in the AnSCs during antler regeneration. Among these 39 genes, the tumor suppressor gene, BRCA1, was found to be more sensitive to DNA damage in the AnSCs compared to that in the deer somatic cells, and BRCA1 deletion in the AnSCs via CRISPR/Cas9 resulted in significantly higher levels of DNA damage. Lack of BRCA1 promoted cell apoptosis and cell senescence and inhibited cell proliferation and cell self-renewal. RNA-seq results showed that in the absence of BRCA1, the p53 signaling pathway was significantly up-regulated. Associated with this change, the cell apoptosis and cell senescence-relevant-genes, CDKN1A, CDKN2A and Fas were over expressed, but the expression of cell-cycle-progression-related genes was inhibited. In addition, BRCA1 expression levels were found to be more sensitive to endoplasmic reticulum stress (ERS) in the AnSCs compared to the somatic cells. Deletion of BRCA1 gene aggravated ERS and ERS-induced cell apoptosis. Conclusions Our results revealed that BRCA1 is involved in sustaining rapid antler growth possibly via promotion of DNA damage repair that acts to maintain genome stability while protecting cells from p53/ERS-induced cell death. Understanding the mechanisms underlying the role played by BRCA1 in the process of antler regeneration is of great significance not only for regenerative medicine, but also for the understanding of cancer development.

Median palatal cyst is a rare nonodontogenic facial cleft cyst. A case of median palatal cyst was admitted to the Department of Otolaryngology, Renji Hospital. A 26-year-old female patient was admitted with ‘repeated bilateral nasal congestion for two years’ and was diagnosed as a median palatal cyst. Endoscopic resection of the cyst at the bottom of the nose plus free nasal septal cartilage transplantation were performed. The wound healed well and the cyst did not recur after one year of follow-up.

Abstract Current climate models suggested that Antarctic sea ice cover would decrease substantially under cumulative CO2 emission, but little is known whether large decrease in Antarctic sea ice can influence the occurrence of strong El Niño. Using time slice coupled and uncoupled model experiments, we show that in response to half reduction of Antarctic sea ice projected near the end of the 21st century, the frequency of strong El Niño would be increased by ~40%. It is contributed by enhanced thermocline, Ekman, and zonal advective positive feedbacks that are partly offset by enhanced thermodynamic damping. The strong warming and weakened westerly winds in the southeastern Pacific generate an anomalous Rossby wave propagating into the eastern subtropical and tropical Pacific, favoring stronger El Nino, and air-sea coupling and ocean feedbacks play a critical role in the teleconnection. Unexpectedly, compare to halved Antarctic sea ice, the ice-free Antarctic leads to a decrease in the frequency of strong El Niño, which is largely due to a substantial increase in thermodynamic damping. We also show that a large portion of the increase of strong El Niño events under greenhouse warming might be connected with Antarctic sea-ice loss, though increased greenhouse gas plays an important role.

Abstract Neural crest cells (NCCs) are central to vertebrate embryonic development, giving rise to diverse cell types with unique migratory and differentiation capacities. This study examines the molecular characteristics of cranial neural crest cell (CNCC)-derived mesenchymal cells, specifically those from teeth which in deer show continuous but limited growth, and antlers, which exhibit remarkable regenerative capabilities. Here, through single-cell RNA sequencing analysis, we uncover shared gene expression profiles between adult antlerogenic and dental mesenchymal cells, indicating common developmental pathways. We identify a striking resemblance in transcriptomic features between antlerogenic progenitor cells and dental pulp mesenchymal cells. Comparative analysis of CNCC-derived and non-CNCC-derived mesenchymal cell pools across species reveals core signature genes associated with CNCCs and their derivatives, delineating essential connections between CNCCs and CNCC-derived adult mesenchymal pools. Furthermore, whole-genome DNA methylation analysis unveils hypomethylation of CNCC derivate signature genes in regenerative antlerogenic periosteum, implying a role in maintaining multipotency. These findings offer crucial insights into the developmental biology and regenerative potential of CNCC-derived mesenchymal cells, laying a foundation for innovative therapeutic strategies in tissue regeneration.

Abstract Plate fixation is a common treatment option for radial head fractures (RHFs). Due to the benefits of less invasiveness and fewer complications of internal fixation, the application of small-diameter headless compression screws (HCSs) to treat RHFs has become a new trend. This study aimed to compare the mechanical stability of four distinct internal fixation protocols for transversely unstable RHFs via finite element analysis. Using computed tomography data from 10 patients, we developed 40 patient-specific FE models of transversely unstable RHFs fixed by parallel, crossed, and tripod HCSs and mini-T plate (MTP). Under simulated physiological loading of the elbow joint, the construct stiffness, displacement, and von Mises stresses were evaluated and verified by a biomechanical experiment. Under shear loading, the MTP group exhibited lower construct stiffness, larger displacement, and higher Von Mises stress than the HCSs group. The stiffness of tripod HCSs was greater than parallel and crossed screw fixation techniques. There was a strong relationship between apparent bone density and construct stiffness (R = 0.98 to 0.99). In the treatment of transversely unstable RHFs, HCSs have superior biomechanical stability than MTP. The tripod technique was also more stable than parallel and crossed fixation.

Abstract Heavy Meiyu-Baiu rainfall can pose threat to the dense population in East Asia by catastrophic flooding. Although previous studies have identified Indian Ocean (IO) warming as the major cause of heavy Meiyu-Baiu rainfall, it failed to predict the record-breaking rainfall in July 2020. Synthesizing observational analysis, large-ensemble climate simulations, and atmospheric simulations, we show that sea-ice loss in the Kara Sea in May can intensify the IO warming-induced heavy Meiyu-Baiu rainfall and well explains the record-breaking rainfall in July 2020. In the precondition of IO warming, sea-ice loss tends to prolong Meiyu-Baiu season and strengthen convective activity over the Meiyu-Baiu region, thereby enhancing the IO warming-induced heavy Meiyu-Baiu rainfall by ~50% and doubling the risk of extreme events comparable to or greater than the one in 2020. A statistical model is further constructed to demonstrate that taking Arctic sea ice into consideration can significantly improve the seasonal prediction of extreme Meiyu-Baiu rainfall.

Diabetic neuropathic pain (DNP) is a common complication of diabetes mellitus (DM) and is characterized by spontaneous pain and neuroinflammation. The Sigma-1 receptor (Sig-1R) has been proposed as a target for analgesic development. It is an important receptor with anti-inflammatory properties and has been found to regulate DNP. However, it is not known whether Sig-1R can ameliorate pathological neuroinflammation in DNP. The present study used a rat model of DNP and a highly selective agonist of Sig-1R to assess the effects of the protein on neuropathic pain in rats with type 2 diabetes mellitus. The rats were divided into Control, Model, Sig-1R agonist PRE-084 (0.3, 0.6, 1 mg/kg), and metformin (Met, 20 mg/kg) groups, with seven rats per group, and their body weight, fasting blood glucose, mechanical withdrawal threshold and thermal withdrawal latency were tested weekly for two weeks. After treatment with PRE-084, the pain thresholds in the DNP rats were significantly improved, together with pathological changes in the dorsal root ganglion, reductions in the serum levels of TNF-α, IL-1β, IL-6, MOD, and prostaglandin E2 (PGE2), and the activity of superoxide dismutase was increased. The mRNA levels of TNF-α, IL-1β, and cyclooxygenase 2 (COX-2) were reduced. Pharmacological inhibition of Sig-1R with BD1047 (10 μM) abolished Sig-1R-mediated activation of lipopolysaccharide-treated BV-2 microglial cells. It was also found that PRE-084 increased phosphorylation of serine/threonine protein kinase B (AKT) and glycogen synthase kinase 3β (GSK-3β) at Ser9, inhibiting nuclear factor kappa B (NF-κB)-mediated neuroinflammation in the dorsal root ganglion, thus reducing DNP. The findings suggest that the effect of Sig-1R agonist PRE-084 on DNP may reduce the level of inflammation through the up-regulation of AKT/GSK-3β and down-regulation of the NF-κB signaling, thereby contributing to the treatment of the disease.

The spectral reflectance provides valuable information regarding vegetation growth and plays an important role in agriculture, forestry, and grassland management. In this study, a small, portable vegetation canopy reflectance (VCR) sensor that can operate throughout the day was developed. The sensor includes two optical bands at 710 nm and 870 nm, with the light separated by filters, and has a field of view of 28°. It is powered by two 14500 rechargeable batteries and uses Wi-Fi for data transmission. The calibration of the sensor was performed using an integrating sphere, and a solar altitude correction model was constructed. The sensor’s accuracy was validated using a standard reflectance gray scale board. The results indicate that the root mean square error (RMSE) and mean absolute error (MAE) at 710 nm were 1.07% and 0.63%, respectively, while those at 870 nm were 0.94% and 0.50%, respectively. Vegetation at 14 sites was measured using both the VCR sensor and an Analytical Spectral Devices (ASD) spectroradiometer at nearly the same time for each site. The results show that the reflectance values measured by both devices were closely aligned. Measurements of Bermuda grass vegetation on clear days revealed that the intra-day reflectance range at 710 nm narrowed from 12.3–19.2% before solar altitude correction to 11.1–13.4% after correction, and the coefficient of variation (CV) decreased from 10.86% to 2.93%. Similarly, at 870 nm, the intra-day reflectance range decreased from 41.6–60.3% to 39.0–42.0%, and the CV decreased from 9.69% to 1.53%. In summary, this study offers a fundamental tool for monitoring vegetation canopy reflectance in the field, which is crucial for advancing high-quality agricultural, grassland, and forest management practices.

Changes in hydrological connectivity not only interfere with the material transfer and energy flow processes within wetland ecosystems or between wetland ecosystems and other ecosystems but also pose potential risks to the ecosystem service functions of wetlands, such as water conservation, climate regulation, and biodiversity maintenance. It is essential to clarify the impacts of changes in hydrological connectivity on wetland habitats to restore wetlands and maintain species diversity. Explaining the effects of changes in hydrological connectivity on wetland habitats is crucial to restoring wetlands and maintaining species diversity. In this paper, we assessed hydrological connectivity and its impacts on wetland habitats based on geostatistical connectivity function and the biohydrological adaptation thresholds of the Naoli River wetland. The results showed that (1) the hydrological connectivity of wetlands within the Naoli River Reserve showed a fluctuating and decreasing trend, and the maximum distance difference between the high and low connectivity periods was 26 km. (2) Waterbirds and macroinvertebrates had a larger area of suitable habitat at moderate hydrological connectivity. At the same time, fish and phytoplankton showed a decrease in the area of suitable habitat with decreasing hydrological connectivity. (3) Hydrological connectivity significantly regulates a high-suitability habitat, and suitable hydrological connectivity increases habitat area by about 35 %. (4) The restoration of hydrological connectivity and suitable habitats should be emphasized in the Trans-Qixing River area, and wetland biodiversity should be maintained according to the hydrological connectivity status in the mainstream area of the Naoli River and the Inner-Qixing River area.

Background: Excessive iron accumulation in the brain has been implicated in Parkinson's disease (PD). However, the patterns and probable sequences of iron accumulation across the PD brain remain largely unknown. This study aimed to explore the sequence of iron accumulation across the PD brain using R2* mapping and a relaxometry covariance network (RCN) approach. Methods: R2* quantification maps were obtained from PD patients (n = 34) and healthy controls (n = 25). RCN was configured on R2* maps to identify covariance differences in iron levels between the two groups. Regions with excessive iron accumulation and large covariance changes in PD patients compared to controls were defined as propagators of iron. In the PD group, causal RCN analysis was performed on the R2* maps sequenced according to disease duration to investigate the dynamics of iron accumulations from the propagators. The associations between individual connections of the RCN and clinical information were analyzed in PD patients. Results: The left substantia nigra pars reticulata (SNpr), left substantia nigra pars compacta (SNpc), and lobule VII of the vermis (VER7) were identified as primary regions for iron accumulation and propagation (propagator). As the disease duration increased, iron accumulation in these three propagators demonstrated positive causal effects on the bilateral pallidum, bilateral gyrus rectus, right middle frontal gyrus, and medial and anterior orbitofrontal cortex (OFC). Furthermore, individual connections of VER7 with the left gyrus rectus and anterior OFC were positively associated with disease duration. Conclusions: Our results indicate that the aberrant iron accumulation in PD involves several regions, mainly starts from the SN and cerebellum and extends to the pallidum and cortices. These findings provide preliminary information on sequences of iron accumulation in PD, which may advance our understanding of the disease.

AbstractBackground and objective Ischaemic encephalopathy is a common cerebrovascular disease caused by insufficient blood supply to the cerebral vessels. The ischaemic encephalopathy is closely associated with the development of many chronic diseases such as obesity, hypertension and diabetes. Neurotrophic therapy has become the main therapeutic strategy for ischaemic encephalopathy. However, neurotrophic drugs only slightly recover the neurological function of patients, and their long-term efficacy is uncertain. Previous reports revealed that the active ingredients of natural medicines play important roles in the treatment of cerebral ischemia. In this study, we reviewed clearing herbs with anti-ischaemic encephalopathy functions using the data from quantitative statistical and network pharmacological exploration methods. We also discussed the different bioactive components and pharmacological effects of these herbs.Methods First, we collected Chinese herbal prescriptions against ischaemic encephalopathy in four databases. Then, we statistically analysed the frequency of application of heat-clearing herbs to obtain the commonly used heat-clearing herbs against ischaemic encephalopathy, and classified them according to their efficacy according to the statistical results, to summarize the mechanism of anti-ischaemic effects of different bioactive components; Second, the network database was used to obtain the above components of heat-clearing Chinese medicines and their corresponding targets of action, disease targets of ischaemic stroke; Venny 2.1.0 was used to obtain component-disease target intersections; Cytoscape was used to construct the ‘Drug-Active Ingredient-Target Network Graph ‘; DAVID was used for GO and KEGG enrichment analysis.Results Literature and database screening involved 149 prescriptions, with a total of 269 flavours of Chinese medicines and 20 flavours of single-flavour heat-clearing Chinese medicines; The top nine in terms of frequency of use were Radix Paeoniae Rubra、Rehmanniae Radix Praeparata、Figwort Root、Cortex Moutan、Scutellariae Radix、Coptidis Rhizoma、Gardeniae Fructus、Cassiae Semen、Lonicerae Japonicae Flos. The common components obtained from network pharmacology were beta-sitosterol, quercetin, and stigmasterol, which mainly act on key targets such as RELA, AKT1, JUN, PRKACA, PTGS2, RAF1 and CHUK; and their active ingredients are mainly involved in signalling pathways such as Calcium, PI3K-Ak, MAPK, cAMP, IL-17, HIF-1, TNF, T-cell receptor, NF-kappa B and JAK-STAT.Conclusions Heat-clearing herbs are useful and promising for the protection against and prevention of ischemic encephalopathy. The results of the network pharmacological studies are similar to the mechanisms of anti-ischemic encephalopathy of the active ingredients of the purgative herbs we have listed; Thin either directly protects cerebrovascular tissues by improving vascular permeability and reducing the area of infarcted tissues, or produces protective effects through molecular signaling pathways. It can be seen that the components of heat-clearing Chinese medicines can exert cerebroprotective effects through multiple pathways, which provides us with a reference for further development and study of heat-clearing Chinese medicines in the treatment of ischemic cerebrovascular diseases.

ABSTRACTInformation on Arctic sea-ice motion in summer is critical for operational sea-ice monitoring and prediction and commercial navigation. Affected by the melting of the sea-ice surface, the accuracy and spatial coverage of the sea-ice velocity (SIV) retrieved by brightness temperature (TB) during the melting period are always lower than in winter. Our research indicates that the lack of ice–water discrimination in summer for the Advanced Microwave Scanning Radiometer 2 (AMSR2) 36 GHz TB is the main reason for the poor quality of its SIV results. We propose a new SIV retrieval scheme based on the polarization difference (P) of the 36 GHz TB. The 36-P SIV has a higher spatial coverage than that derived from 18-H, 36-H and 36-V SIVs and a higher maximum cross-correlation coefficient than 36 GH TB-derived SIVs. Compared with buoy and Synthetic Aperture Radar SIVs, the 36-P SIV’s error is close to that of 18-H SIV and significantly lower than that of 36 TB SIV. Therefore, our results indicate that 36-P is more competitive than the 36 GHz TB in SIV retrieval in summer. Further analysis shows that our proposed scheme is compatible with the two current mainstream SIV tracking algorithms, demonstrating its great potential for future summer SIV retrieval.

Dendritic cells, which are crucial for inducing T-cell responses, are pivotal in current immunotherapy strategies aiming to replenish depleted T cells within the tumor microenvironment to combat tumors. Consequently, dendritic cell vaccine-based cancer therapies have garnered significant attention. Through bibliometric analysis, we examined research trends in this field. We searched the Web of Science core database and identified 16,476 articles on dendritic cell-based vaccines published from January 1, 2009, to December 30, 2023. The United States leads in this research domain, with Emory University being a prominent collaborator. The Journal of Immunology is the primary publication outlet, and Banchereau, J emerges as the most influential author. Recent hot keywords include nanoparticle, delivery, cancer vaccine, and clinical trial, indicating that cancer immunotherapy research, especially dendritic cell-based vaccines, is poised to become a future trend and hotspot.

Rapid decline in Arctic summer sea ice cover has brought new opportunities for shipping and resource exploitation in the Arctic, and accurate determination of summer sea ice conditions has become increasingly important. Knowledge of sea ice velocity (SIV) is crucial for ice engineering and navigation in the Arctic. This study retrieved SIV in summer based on the polarization difference (PD) of brightness temperatures (TBs) at 36 GHz derived from the recalibrated FY-3D satellite microwave radiometer data FY-3D/MWRI. Compared with swath TB data, swath PD data can better suppress the noise associated with atmospheric wetness (cloud liquid water and water vapor). Moreover, different from the arbitrary template selection scheme used in current algorithms, we propose an optimized template selection scheme based on the image texture, which considers the frequent deformation processes of sea ice in summer. Determination of SIV using templates with irregular distribution presents lower uncertainty and higher computational efficiency compared with templates with regular distribution. Based on the improved algorithm, this study obtained either swath irregular SIV fields with nominal spatial resolution of 30 km or daily gridded SIV fields with 50-km spatial resolution in summer 2019 using 36-GHz PDs.

Abstract In this study, we investigate the climatology and trend of explosive cyclones (ECs) over the Southern Ocean (50oS–70oS) during 1980–2020 by combining a method that is most suited for identifying and tracking cyclones in the Southern Ocean and a latest climate reanalysis. On average, approximately 50 ECs are generated annually over the Southern Ocean, with a significant increasing trend of 2.3 per decade during the studying period. This increasing trend is dominated by the trend of strong ECs, particularly in autumn. We analyze the dynamical and thermodynamical effects associated with multiple deepened strong ECs in autumn over an identified key region in the southern Pacific Ocean sector (155oW–170oW, 50oS–65oS), where the density of the initiation of ECs shows the largest increasing trend in autumn. The composite analysis reveals the general patterns and duration of the effects on the atmosphere, ocean, and sea ice associated with multiple ECs in the southern Pacific Ocean. The results indicate that the deepened strong ECs are associated with significant changes in meridional winds, downward longwave radiation, and sensible and latent heat fluxes. These changes lead to cold sea surface temperature anomalies in the northeast of the key region, reaching a maximum 5–7 days after the EC deepening, and the increased sea ice cover south of the key region, peaking 4–5 days after the EC deepening.

【Objective】The study is carried out to explore the effect of mulberry leaf feeding on the growth and development of Spodoptera frugiperda, with an aim to provide a theoretical basis and reference for the potential damage of mulberry gardens caused by S. frugiperda.【Method】The populations of S. frugiperda feeding on artificial diet and mulberry leaves were established by two-sex life tables, and the growth & development and reproductive indexes were measured, including the development duration, oviposition amount, pupal weight and pupation rate. And the population parameters were calculated with the two-sex life table software TWOSEX-MS Chart 2024, followed by ANOVA and graphing. Finally, TIMING-Mschart was used to predict the future 90 d population dynamics of S. frugiperda feeding on artificial diet and mulberry leaves.【Result】The total developmental durations of S. frugiperda feeding on mulberry leaves and artificial diet were 44.18 (±0.93) and 32.30 (±0.26) d, the larval survival rates were 41.17 (±5.88)% and 55.56 (±12.73)%, the pupal weight were 174.4 (±34.2) and 225.9 (±23.7) mg per pupa, the oviposition amounts of single female moth were 499.58 (±278.67) and 877.40 (±440.79), and both of the pupation rate were 100%. The intrinsic rates of increase of S. frugiperda feeding on mulberry leaves and artificial diet were 0.10 (±0.01) and 0.14 (±0.01) per day, finite rates of increase were 1.11 (±0.01) and 1.16 (±0.01) per day, net reproduction rates were 128.57 (±36.37) and 250.64 (±77.14) eggs per single female moth, and mean generation times were 47.03 (±1.42) and 37.86 (±0.34) days, respectively.【Conclusion】S. frugiperda feeding on mulberry leaves and artificial diet could complete the generation development, and compared with feeding on artificial diet, the growth and development rate of S. frugiperda feeding on mulberry leaves is slower, and the developmental uniformity, the survival rate, and oviposition amount are all lower. In conclusion, under natural conditions, when the population density is too large or the most suitable host plant is insufficient, it may pose a threat for S. frugiperda larvae to live on mulberry leaves.

The scarcity of public resources and environmental pollution caused by rapid urbanization highlight the practical significance of parks in ensuring the sustainable development of a city. Therefore, the social equity of parks warrants further study. This paper proposes a fine-grained comprehensive evaluation framework that combines geographic accessibility models, geo-statistical analysis, and machine learning algorithms to explore social inequity in Taiyuan, China. In this framework, gini coefficient and lorentz curve express spatial equality, accessibility shows spatial equity, and ridge regression model handles the interdependence of variables with different dimensions to quantify the relative effects of local participants on changes in park accessibility. On this basis, the imbalance between vulnerable groups and park supply is analyzed to further understand the core concept of social equity. Results highlight serious spatial inequality in all three types of parks allocation of six urban areas, especially in community parks. The actual access level of people to parks is also stratified by their demographic and socioeconomic characteristics, revealing the social inequity in access to parks. Park distribution is indeed not conducive to some social vulnerable groups, whose contradiction between supply and demand is highly prominent in urban – rural junctions and new urban areas. This paper also confirms the unfair layout of public facilities can be observed in second-tier cities of China by highlighting the social inequity of parks in Taiyuan. The findings of this work have profound implications for urban planning and sustainable development.

Sea buckthorn (Hippophae rhamnoides L.) contains a variety of biologically active compounds, including flavonoids, terpenoids, polysaccharides, organic acids, volatile oils, and vitamins. It has been demonstrated to be effective in the treatment of cardiovascular disorders. In this paper, we evaluated the pharmacological effects of sea buckthorn in cardiovascular diseases through preclinical studies, and revealed the mechanism of action of the active components in sea buckthorn in cardiovascular diseases, including anti-inflammatory, lipid oxidation regulation, antioxidant, vascular function modulation, anti-platelet aggregation, autophagy, intestinal microorganism regulation, and cell apoptosis reduction. In clinical trials, sea buckthorn was proven to be effective in managing lipid metabolism, blood pressure, and blood glucose levels in patients. We also extensively reviewed the safety of sea buckthorn medicine and its toxicity to numerous organs. To summarize, sea buckthorn has a beneficial effect on cardiovascular disease and may give a novel strategy for clinical intervention and therapy. This paper summarizes the phytochemistry, pharmacology, clinical applications, safety, and toxicity of sea buckthorn in order to better understand the mechanism of action of the various bioactive components in sea buckthorn, investigate its medicinal potential, and provide more options for the treatment of cardiovascular diseases.

Abstract Ovarian cancer is high recurrence and mortality malignant tumor. The most common ovarian cancer was High‐Grade Serous Ovarian Cancer. However, High‐Grade Serous Ovarian Cancer organoid is rare, which organoid with patient immune microenvironment and blood vessels even absence. Here, we report a novel High‐Grade Serous Ovarian Cancer organoid system derived from patient ovarian cancer samples. These organoids recapitulate High‐Grade Serous Ovarian Cancer organoids' histological and molecular heterogeneity while preserving the critical immune microenvironment and blood vessels, as evidenced by the presence of CD34+ endothelial cells. Whole exome sequencing identifies key mutations (CSMD3, TP53, GABRA6). Organoids show promise in testing cisplatin sensitivity for patients resistant to carboplatin and paclitaxel, with notable responses in cancer proteoglycans and p53 (TP53) signaling, like ACTG/ACTB1/AKT2 genes and BBC3/MDM2/PERP. Integration of immune microenvironment and blood vessels enhances potential for novel therapies like immunotherapies and angiogenesis inhibitors. Our work may provide a new detection system and theoretical basis for ovarian cancer research and individual therapy.

Abstract Compound warm extremes exert profound impacts on environment, health, and socioeconomics. Yang et al. (2024) indicated a shift or transition from warm‐dry extremes (WDEs), common in non‐ice‐covered areas, to warm‐wet extremes (WWEs) in ice‐covered zones. Utilizing ERA5 reanalysis data, this study determined the duration and frequency of WDEs and WWEs across ice‐covered and non‐ice‐covered regions. A comprehensive analysis uncovers the physical mechanisms responsible for the paradigm differences and attributes them to the weakening of land‐atmosphere interaction caused by ice‐cover, which inhibits soil moisture feedback and reduces the intensity and duration of warm events in ice‐covered areas. Both WDEs and WWEs are associated with high‐pressure systems (HPs). WDEs, situated directly beneath HPs, intensify due to adiabatic warming from subsidence motions. Conversely, WWEs, located beneath the poleward fringes of HPs, emerge from advective warming and moistening associated with poleward intrusions of warm‐moist air.

Abstract Mulberry bacterial wilt is a devastating disease that is difficult to control and causes serious economic losses to the sericulture industry. This disease is mostly caused by a diverse group of pathogenic and opportunistic bacteria including, Ralstonia pseudosolanacearum, Pantoea ananatis, Enterobacter cloacae complex (ECC), Klebsiella pneumoniae species complex (KpSC), and K. oxytoca complex (KoC). Due to the lack of a rapid and reliable test to simultaneously detect these complex pathogens of mulberry wilt, we developed a multiplex PCR (mPCR) assay to detect five virulence-related genes carried by the pathogenic bacteria of mulberry bacterial wilt disease. The primers were designed for the virulence-related genes: pleD (GGDF structural domain-containing protein), yjfP (esterase), pelY (peripheral pectate lyase), ampD (N-acetyl-anhydromuranmyl-L-alanine amidase), and ripW (type III effector). Overall, the developed mPCR assay showed highly specific, sensitive and reproducible detection of target pathogens. Briefly, the results showed that the mPCR was highly specific in individual reactions, and the lowest detection concentration of the five pathogenic bacteria was 1.87 × 103 CFU/mL (DNA = 2.45 pg/μL). From 46 natural mulberry wilt samples, the mPCR detection rates of P. ananatis, ECC, KpSC, KoC and R. pseudosolanacearum were 8.69, 91.3, 34.7, 23.9 and 65.21%, respectively. The traditional culture media isolation methods showed comparable results. The pathogenicity test of 84 suspected pathogenic bacteria revealed that the morbidity (average morbidity level) caused by the pathogenic bacteria detected by mPCR was ≥ 65.5%, while the morbidity of the undetected pathogenic bacteria was ≤ 35.5%. Based on these results, we believe that the mPCR developed in the present study will be useful in rapid, reproducible, and sensitive detection of the pathogenic bacteria causing mulberry bacterial wilt including, R. pseudosolanacearum, P. ananatis, ECC, KpSC, and KoC. Graphical abstract

Here, wire-arc additive manufacturing (WAAM) is employed to fabricate Al–Ce–Mg heat-resistant aluminum alloy, considering its capability to manufacture large complex structures more efficiently. Large-sized faceted Al11Ce3 intermetallic compounds are formed in the as-cast alloy with a hypereutectic microstructure. The microstructure is transformed to a eutectic microstructure by non-equilibrium solidification of WAAM, consisting lamellar α-Al/A111Ce3 eutectics. The WAAM alloy shows enhanced mechanical strength and ductility at 200 °C, compared with the as-cast alloy. The significant improvements of ultimate tensile strength and elongation for the WAAM alloy are correlated with its higher strain hardening rate, along with the transition from cleavage fracture to dimple fracture. The cracking of All1Ce3 particles occurs preferentially during the elastic deformation stage, as revealed by in-situ testing, and the strain hardening capability of the as-cast alloy is reduced. Pore defects, 0.15 % in volume fraction, are produced via WAAM processing, and the plastic deformation promotes the pore growth and mergence, increases the pore volume fraction, and decreases the pore sphericity. Our results demonstrate that WAAM is strongly attractive for the fabrication of Al–Ce–Mg alloys, due to the enhanced high-temperature strength-ductility synergy.

Abstract During growth phase, antlers exhibit a very rapid rate of chondrogenesis. The antler is formed from its growth center reserve mesenchyme (RM) cells, which have been found to be the derivatives of paired related homeobox 1 (Prrx1)-positive periosteal cells. However, the underlying mechanism that drives rapid chondrogenesis is not known. Herein, the miRNA expression profiles and chromatin states of three tissue layers (RM, precartilage, and cartilage) at different stages of differentiation within the antler growth center were analyzed by RNA-sequencing and ATAC-sequencing. We found that miR-140-3p was the miRNA that exhibited the greatest degree of upregulation in the rapidly growing antler, increasing from the RM to the cartilage layer. We also showed that Prrx1 was a key upstream regulator of miR-140-3p, which firmly confirmed by Prrx1 CUT&Tag sequencing of RM cells. Through multiple approaches (three-dimensional chondrogenic culture and xenogeneic antler model), we demonstrated that Prrx1 and miR-140-3p functioned as reciprocal negative feedback in the antler growth center, and downregulating PRRX1/upregulating miR-140-3p promoted rapid chondrogenesis of RM cells and xenogeneic antler. Thus, we conclude that the reciprocal negative feedback between Prrx1 and miR-140-3p is essential for balancing mesenchymal proliferation and chondrogenic differentiation in the regenerating antler. We further propose that the mechanism underlying chondrogenesis in the regenerating antler would provide a reference for helping understand the regulation of human cartilage regeneration and repair.

Abstract Response coordination design becomes an inevitable trend based on the multidisciplinary optimization design (MOD) in the development of the design for complex mechanical structures. Aiming at the problem of unclear mechanism of response coordination for main loaded structures, a response coordination design technology characterized by a response coordination evaluation system is proposed based on an analytic hierarchy process. In addition, a nondominated sorting elephant herding optimization (NSEHO) algorithm is proposed by introducing the Pareto optimization theory into elephant herding optimization and combining fixed‐sized candidate set adaptive random testing algorithm to overcome inherent limitations of the traditional algorithm in response coordination design. Taking the main bearing assembly structure as an example, the response coordination design is conducted based on the proposed technology and NSEHO algorithm. The response coordination design scheme of the main bearing assembly structure is experimentally verified. The results show that the Pareto frontier of NSEHO is smoother and is closer to the real Pareto frontier compared to NSGA‐II in condition of small population size and restricted iteration generations, revealing the advancement of the solving ability of NSEHO. The coordination coefficients of strength, stiffness, contact strength, and mass of the main bearing assembly structure are increased by 13.91%, 14.96%, 2.63%, and 0.07%, respectively, and the overall coordination coefficient are increased by 11.10%. The indicators of strength, stiffness, and contact strength of the response coordination scheme are better than those of the original scheme by experimental verification, demonstrating the effectiveness of the response coordination design technology. The proposed technology reveals the response coordination mechanism of the main loaded structures of internal combustion engines and provides an important guiding significance to MOD for complex mechanical structures.

Maize (Zea mays L.) is an economically vital grain crop that is cultivated worldwide. In 2011, a maize foliar disease was detected in Lingtai and Lintao counties in Gansu Province, China. The characteristic signs and symptoms of this disease include irregular chlorotic lesions on the tips and edges of infected leaves and black punctate fruiting bodies in dead leaf tissues. Given favourable environmental conditions, this disease spread to areas surrounding Gansu. In this study, infected leaves were collected from Gansu and Ningxia Hui Autonomous Region between 2018 and 2020 to identify the disease-causing pathogen. Based on morphological features, pathogenicity tests, and multi-locus phylogenetic analysis involving internal transcribed spacer (ITS), 18S small subunit rDNA (SSU), 28S large subunit rDNA (LSU), translation elongation factor 1-alpha (TEF), and β-tubulin (TUB) sequences, Eutiarosporella dactylidis was identified as the causative pathogen of this newly discovered leaf blight. Furthermore, an in vitro bioassay was conducted on representative strains using six fungicides, and both fludioxonil and carbendazim were found to significantly inhibit the mycelial growth of E. dactylidis. The results of this study provide a reference for the detection and management of Eutiarosporella leaf blight.

Macrolide pollution has attracted a great deal of attention because of its ecotoxic effects on microalgae, but the role of phycospheric bacteria under antibiotic stress remains unclear. This study explored the toxic effects of erythromycin (ERY) on the growth and nitrogen metabolism of Auxenochlorella pyrenoidosa; then, it analyzed and predicted the effects of the composition and ecological function of phycospheric bacteria on microalgae under ERY stress. We found that 0.1, 1.0, and 10 mg/L ERY inhibited the growth and chlorophyll of microalgae, but the microalgae gradually showed enhanced growth abilities over the course of 21 days. As the exposure time progressed, the nitrate reductase activities of the microalgae gradually increased, but remained significantly lower than that of the control group at 21 d. NO3− concentrations in all treatment groups decreased gradually and were consistent with microalgae growth. NO2− concentrations in the three treatment groups were lower than those in the control group during ERY exposure over 21 d. ERY changed the community composition and diversity of phycospheric bacteria. The relative abundance of bacteria, such as unclassified-f-Rhizobiaceae, Mesorhizobium, Sphingopyxis, Aquimonas, and Blastomonas, varied to different degrees. Metabolic functions, such ABC transporters, the microbial metabolism in diverse environments, and the biosynthesis of amino acids, were significantly upregulated in the treatments of higher concentrations (1.0 and 10 mg/L). Higher concentrations of ERY significantly inhibited nitrate denitrification, nitrous oxide denitrification, nitrite denitrification, and nitrite and nitrate respiration. The findings of this study suggest that phycospheric bacteria alleviate antibiotic stress and restore the growth of microalgae by regulating nitrogen metabolism in the exposure system.

BackgroundNurses’ competencies are crucial for infectious disease prevention and control. We aimed to investigate competencies in responding to infectious disease outbreaks of nurses in primary healthcare institutions and identify their training needs.MethodsA cross-sectional study was conducted from June to September 2022, recruiting nurses from primary healthcare institutions across Sichuan Province. Their competencies and training needs were assessed using a modified Emergency Response Competency Scale for Infectious Diseases. Additionally, their sociodemographic characteristics and experience in infectious disease outbreak trainings were collected. Univariate analyses were used to compare competencies and training needs by participant characteristics. Multiple linear regression was conducted to identify determinants of their competencies.ResultsA total of 1,439 nurses from 44 primary healthcare institutions participated in this study. The overall competency and training needs had a median of 3.6 (IQR [3.1, 4.0]) and 4.0 (IQR [3.9, 4.7]), respectively. Age (β = −0.074, p = 0.005), experience in higher authority hospitals (β = 0.057, p = 0.035), infectious disease outbreak trainings attended within the last 5 years (β = 0.212, p

Background No studies have investigated whether high-sensitivity C reactive protein (hsCRP) can be used to predict the forced expiratory volume in 1 s (FEV1)/estimated value of FEV1 (FEV1%pred). This study aimed to assess the association between hsCRP and FEV1%pred in middle-aged and elderly individuals without underlying lung disease.Methods The data for this study were obtained from a prospective cohort study that included 1047 middle-aged and elderly citizens from Beijing aged 40–75 years without any evidence of underlying lung diseases with FEV1 >70% after receiving inhalational bronchodilators. The baseline analysis of the participants was performed from 30 May 2018 to 31 October 2018. Restricted cubic spline regression and multivariate linear regression models were used to assess the non-linear association and linear association between hsCRP and FEV1/FEV in 6 s (FEV6) and FEV1%pred, respectively.Results The hsCRP values of 851 participants were recorded; the values were normal in 713 (83.8%) participants. The remaining 196 participants (18.7%) had missing data. A non-linear association was observed between normal hsCRP values and FEV1/FEV6. hsCRP was linearly and negatively correlated with FEV1%pred, and each 1 SD increase in hsCRP was significantly associated with a 2.4% lower in FEV1%pred. Significantly higher FEV1/FEV6 differences were observed in the female subgroup than those in the male subgroup (p=0.011 for interaction).Conclusions hsCRP had a non-linear association with FEV1/FEV6 and a linear negative association with FEV1%pred in individuals with normal hsCRP values. hsCRP can be used to predict FEV1%pred, which can be used to predict the development of chronic obstructive pulmonary disease. hsCRP has a stronger association with lung function in women than that in men.Trial registration number NCT03532893.

Abstract This study investigates the specific circulation anomalies that have sustained the low Antarctic sea ice state since 2016. Firstly, we find a significant strengthening and southward shift in the Ferrel Cell (FC) during 2016–2022, resulting in a marked increase in southward transport of heat and moisture. Secondly, this enhanced FC is closely associated with a stronger mid‐latitude wave pattern. This pattern is zonally asymmetric and greatly amplifies the poleward advections of heat and moisture, leading to the increased downward longwave radiation, more liquid precipitation and sea ice retreat in specific regions, including the western Pacific and Indian Ocean sectors, Ross and northern Weddell Seas. The mechanism deduced from the short‐term period is further supported by the results of 40 ensemble members of simulations. The southward expansion of the FC and sea ice decline are closely linked to La Niña‐like conditions but may also be driven by anthropogenic global warming.

BackgroundPebrine, caused by microsporidium Nosema bombycis, is a devastating disease that causes serious economic damages to the sericulture industry. Studies on development of therapeutic and diagnostic options for managing pebrine in silkworms are very limited. Methionine aminopeptidase type 2 (MetAP2) of microsporidia is an essential gene for their survival and has been exploited as the cellular target of drugs such as fumagillin and its analogues in several microsporidia spp., including Nosema of honeybees.MethodsIn the present study, using molecular and bioinformatics tools, we performed in-depth characterization and phylogenetic analyses of MetAP2 of Nosema bombycis isolated from Guangdong province of China.ResultsThe full length of MetAP2 gene sequence of Nosema bombycis (Guangdong isolate) was found to be 1278 base pairs (bp), including an open reading frame of 1,077 bp, encoding a total of 358 amino acids. The bioinformatics analyses predicted the presence of typical alpha-helix structural elements, and absence of transmembrane domains and signal peptides. Additionally, other characteristics of a stable protein were also predicted. The homology-based 3D models of MetAP2 of Nosema bombycis (Guangdong isolate) with high accuracy and reliability were developed. The MetAP2 protein was expressed and purified. The observed molecular weight of MetAP2 protein was found to be ~43–45 kDa. The phylogenetic analyses showed that MetAP2 gene and amino acids sequences of Nosema bombycis (Guangdong isolate) shared a close evolutionary relationship with Nosema spp. of wild silkworms, but it was divergent from microsporidian spp. of other insects, Aspergillus spp., Saccharomyces cerevisiae, and higher animals including humans. These analyses indicated that the conservation and evolutionary relationships of MetAP2 are closely linked to the species relationships.ConclusionThis study provides solid foundational information that could be helpful in optimization and development of diagnostic and treatment options for managing the threat of Nosema bombycis infection in sericulture industry of China.

Objective: To investigate the therapeutic effect of palmar ginseng on cognitive impairment in rats with type 2 diabetes, evaluate its neuroprotective effects, and explore its underlying mechanism. Methods: A rat model of diabetic cognitive impairment (DCI) was established by feeding with homemade high-fat, high-sugar chow combined with intraperitoneal injection of streptozotocin (STZ). Rats were continually fed high-fat, high-sugar chow for 60 days after successful induction of the model. Palmar ginseng was administered via gavage. The Morris test was performed after 30 days of treatment. At the end of the test, blood samples were collected, and the activities of IL-6, IL-10, TNF-α, and IL-1β in rat serum. Pathological changes in hippocampal tissues were observed by Haematoxylin–eosin (HE) staining of the brain, activation of microglia in hippocampal tissues was detected by immunofluorescence, and the expression of PI3K/Akt/mTOR and JAK2/STAT3 proteins in the hippocampal tissues by Western blot. Results: During the administration of palmar Ginseng, the body weight and blood glucose levels of DCI rats were measured weekly, with results showing that Palmar Ginseng effectively reduced blood glucose levels and body weight of DCI rats. Behavioural tests in the water maze indicated that palmar ginseng effectively improved the learning and memory ability of DCI rats. HE and immunofluorescence staining showed that palmar ginseng improved DCI in rats, ameliorated hippocampal neuronal damage, and improved microglial activation. ELISA showed that palmar ginseng significantly reduced the expression of pro-inflammatory factors in the serum of DCI rats. Increased expression of anti-inflammatory factors was observed, and Western blot analysis showed that Palmar Ginseng regulated PI3K/Akt/mTOR and JAK2/STAT3 protein expression, promoted the phosphorylation of PI3K/Akt/mTOR, and inhibited JAK2/STAT3 protein phosphorylation in rat hippocampal tissues as well as in BV2 cells. Conclusions: Palmar ginseng may improve the onset and development of DCI by upregulating the phosphorylation of proteins in the PI3K/Akt/mTOR pathway.

Objectives Career self-management is believed to be a critical behaviour in the new career era. However, the underlying mechanisms that stimulate nurses’ career self-management are unclear. The aim of this study was to examine the mediating effect of self-efficacy and the moderating effect of proactive personality on the relationship between perceived organisational support and career self-management among nurses.Design This was a cross-sectional survey.Setting and participants A total of 1866 nurses from 15 hospitals across 15 cities in China were recruited for this study.Primary and secondary outcome measures The Perceived Organizational Support Scale, General Self-efficacy Scale, Proactive Personality Scale and Individual Career Management Questionnaire were used. Data were analysed using moderated mediation regressions with Hayes’ PROCESS macro in SPSS version 26.0.Results General self-efficacy mediated the relationship between perceived organisational support and career self-management. Proactive personality moderated the direct (B=0.043, p

Abstract Background Allergic rhinitis (AR) is a prevalent immune-related allergic disease, and corticosteroid nasal sprays serve as the primary treatment for this patient population. However, their short duration of efficacy and frequent administration pose challenges, leading to drug wastage and potential adverse effects. To overcome these limitations, we devised a novel approach to formulate DEX-Gel by incorporating dexamethasone (DEX) into a blend of Pluronic F127, stearic acid (SA), and polyethylene glycol 400 (PEG400) to achieve sustained-release treatment for AR. Results Following endoscopic injection into the nasal mucosa of AR rats, DEX-Gel exhibited sustained release over a 14-day period. In vivo trials employing various assays, such as flow cytometry (FC), demonstrated that DEX-Gel not only effectively managed allergic symptoms but also significantly downregulated helper T-cells (TH) 2 and TH2-type inflammatory cytokines (e.g., interleukins 4, 5, and 13). Additionally, the TH1/TH2 cell ratio was increased. Conclusion This innovative long-acting anti-inflammatory sustained-release therapy addresses the TH1/TH2 immune imbalance, offering a promising and valuable approach for the treatment of AR and other inflammatory nasal diseases. Graphical Abstract

Owing to operating condition switching and internal degradation mechanisms, the degradation processes of some lithium-ion batteries (LIBs) exhibit non-monotone and two-phase patterns, which are composed of a linear first phase and a nonlinear second phase. The existing Gamma process and Inverse Gaussian process methods are limited to modeling the monotone degradation data. Besides, traditional single-phase nonlinear models and two-phase linear models are insufficient to describe such a degradation process effectively. Therefore, degradation modeling and remaining useful life (RUL) prediction of the hybrid deteriorating LIBs is still a compelling practical issue. In this paper, a two-phase hybrid degradation model with a linear first phase and a nonlinear second phase is formulated based on the widely used Wiener process-based model. Taking into account the random effects caused by the unit heterogeneity and the uncertainty of the degradation state at the changing point, we obtain the analytical solutions of the lifetime estimation and RUL prediction under the concept of the first passage time (FPT). In addition, to conduct model parameter identification, the expectation maximization (EM) algorithm in conjunction with a profile log-likelihood function method are utilized for offline parameter estimation. Subsequently, the Bayesian rule is adopted to conduct the online parameter updating. Finally, the numerical and practical experiments are provided for verification and show that the proposed method could achieve high estimation accuracy for the RUL prediction of the two-phase hybrid deteriorating LIBs.

Isolated marsh wetlands are crucial for maintaining regional hydrological connectivity and biological contiguity. The Sanjiang Plain is the most typical area of marsh wetland change in China. A large number of isolated marshy wetlands have been formed here due to natural and anthropogenic influences. However, there have been few quantitative studies of the dynamics of isolated marsh wetlands and their drivers at the regional scale. This study used Landsat series image data provided by the Google Earth Engine. Through field surveys, combined with visual interpretation and the Random Forest Algorithm, the distributional changes in isolated marsh wetlands, non-isolated marsh wetlands, and natural marsh wetlands in the Sanjiang Plain from 1975 to 2020 were identified and extracted. The dynamic change characteristics as well as the patch importance values (dIIC) of isolated and non-isolated marsh wetlands were analyzed using the dynamic degree, standard deviation ellipse model, and the integral index of connectivity (IIC). Finally, the driving factors and interactions affecting the distribution of isolated marsh wetlands were analyzed by the Geodetector model. The results show that (1) the temporal dynamics of the three types of marsh wetlands are less than 0 from 1975 to 2020, and the temporal dynamics of isolated marsh wetlands are the largest. The lost wetlands were concentrated in the northeastern and east–central regions of the Sanjiang Plain. The center of mass of the standard deviation ellipse moved from northeast to southwest, and the isolated marsh wetlands moved the most. (2) The IIC of non-isolated marsh wetlands and natural marsh wetlands decreased and then increased, and the non-isolated marsh wetlands with high-grade connectivity were mainly distributed in the northeastern and east–central regions. On the other hand, the IIC of isolated marsh wetlands increased and then decreased, and the isolated marsh wetlands with high-grade connectivity were mainly distributed in the northeastern region. (3) The elevation is the most important driving factor affecting the distribution of isolated marsh wetlands in the Sanjiang Plain. The interaction between the driving factors had a significantly higher effect on the distribution of isolated marsh wetlands than that of a single driving factor, with the strongest interaction between aspect and elevation in 1975, 1986, 2000, and 2010, and between aspect and slope in 2020.

Background/Objectives: Breast cancer, a leading health threat affecting millions worldwide, requires effective therapeutic interventions. Celastrol (CEL), despite its antitumor potential, is limited by poor solubility and stability. This study aimed to enhance CEL’s efficacy by encapsulating it within glycyrrhizic acid (GA)-modified lipid calcium carbonate (LCC) nanoparticles for targeted breast cancer therapy. Methods: The 4T1 mouse breast cancer cells were used for the study. GA-LCC-CEL nanoparticles were prepared using a gas diffusion method and a thin-film dispersion method. GA-LCC-CEL were characterized using the zeta-potential, dynamic light scattering and transmission electron microscope (TEM). The in vitro release behavior of nanoparticles was assessed using the in vitro dialysis diffusion method. Cellular uptake was examined using flow cytometry and confocal microscopy. Intracellular ROS and Rhodamine 123 levels were observed under fluorescence microscopy. MTT and colony formation assays assessed cytotoxicity and proliferation, and apoptosis was analyzed by Annexin V-FITC/PI staining. Wound healing and transwell assays evaluated migration, and Western blotting confirmed protein expression changes related to apoptosis and migration. Results: GA-LCC-CEL nanoparticles displayed a well-defined core-shell structure with a uniform size distribution. They showed enhanced anti-proliferative and pro-apoptotic effects against 4T1 cells and significantly reduced breast cancer cell invasion and migration. Additionally, GA-LCC-CEL modulated epithelial-mesenchymal transition (EMT) protein expression, downregulating Snail and ZEB1, and upregulating E-cadherin. Conclusions: GA-LCC-CEL nanoparticles represent a promising targeted drug delivery approach for breast cancer, enhancing CEL’s antitumor efficacy and potentially inhibiting cancer progression by modulating EMT-related proteins.

Improving seed germination and seedling development can potentially increase crop yield and improve quality in direct-seeded rice. This study aimed to detect loci or genes associated with rice seed germination. We reported the phenotypic analysis of seed germination in 103 rice accessions across two years, and a genome-wide association study (GWAS) was conducted to identify loci underlying the genetic regulation of seed germination. A total of seven genetic loci were found to be associated with seed germination, including five loci that overlapped with the previously reported loci/genes, and two novel loci. Of these, two loci (qGP2 and qGP4.1) were stable across different environments. GP4 (Germination percentage 4), encoding a 9-cis-epoxycarotenoid dioxygenase, was identified as the candidate gene of the major locus qGP4.1. A sequence analysis of GP4 revealed that four functional polymorphic sites in the coding region were significantly associated with germination percentage. The disruption of GP4 by gene editing resulted in faster seed germination and seedling establishment. Taken together, we have identified GP4 as a novel gene involved in rice seed germination, and we provide a potential target gene for improving rice seed vigor via gene editing or molecular breeding.

Abstract Introduction The typical outcome of mammalian wound healing is scarring, a fibrotic process mediated by myofibroblast aggregation. Perfect healing in a clinical setting is relatively unexplored. Surprisingly, our previous studies have shown that the large wound (10 cm diameter or more) of the pedicle of deer naturally achieves regenerative restoration, realized through a paracrine pathway from adjacent antler stem cells (AnSCs). Methods AnSC-derived exosomes (AnSC-exos) were topically injected around the full-thickness wounds in a rat model. The effects on the rate of wound healing and the quality of healing were evaluated via morphological, histological, and molecular biological techniques on days 14 and 28 after surgery. Results The results showed that AnSC-exos significantly accelerated the rate of wound healing and improved healing quality, including regeneration of cutaneous appendages (hair follicles and sebaceous glands) and the distribution pattern of collagen (basket-weave-like) in the healed skin. These effects of AnSC-exos were comparable to those of AnSCs but were significantly more potent than those of exosomes derived from bone marrow mesenchymal stem cells (bMSC-exos). Furthermore, AnSC-exos treatment effectively inhibited fibroblast-to-myofibroblast transition (FMT), as evidenced by the reduction of full-thickness skin injury-induced FMT in vivo and TGF-β1-induced FMT in vitro. Conclusion AnSC-exos could effectively promote regenerative cutaneous wound healing, highly likely through FMT inhibition. This suggests that AnSC-exos treatment could provide the potential for a novel approach to induce regenerative wound healing in the clinical setting. Graphical Abstract

Abstract Pulmonary fibrosis (PF), a chronic interstitial lung disease, is characterized by over-abundant deposition of extracellular matrix consisting mainly of collagen I. In previous studies, we demonstrated that deer antler stem cells (AnSCs), a novel type of adult stem cell, are capable of significantly down-regulating collagen formation in different organs and tissues and speculated that they could effectively treat PF via reducing collagen deposition in the lung tissue. In the present study, we found that administration of AnSCs improved the survival rate of PF mice and reduced lung fibrosis, collagen deposition and myofibroblast differentiation. The effects of AnSC treatment were significantly better than the positive control (adipose-derived stem cells). Interestingly, AnSC-Exos were almost equally effective as AnSCs in treating PF, suggesting that the effects of AnSCs on reduction of PF may be mainly through a paracrine mechanism. Further, AnSC-Exos reduced the number of M2 macrophages, a type of macrophage that secrets pro-fibrotic factors to accelerate fibrotic progression, in the lung tissues. In vitro experiments showed that the effects of AnSC-Exos on macrophage modulation were likely achieved via inhibition of the recruitment of circulating monocyte-derived macrophages (reducing the number of macrophages), rather than via inhibition of M2 polarization of macrophages. Inhibition of macrophage recruitment by AnSCs may be achieved indirectly via inhibiting CCL7 expression in fibroblasts; both let-7b and let-7a were highly enriched in AnSC-Exos and may play a critical role in the inhibition of CCL7 expression of fibroblasts. Collectively, the use of antler stem cells or their exosomes opens up a novel strategy for PF treatment in the clinical setting.

In the last decade, organoid research has entered a golden era, signifying a pivotal shift in the biomedical landscape. The year 2023 marked a milestone with the publication of thousands of papers in this arena, reflecting exponential growth. However, amid this burgeoning expansion, a comprehensive and accurate overview of the field has been conspicuously absent. Our review is intended to bridge this gap, providing a panoramic view of the rapidly evolving organoid landscape. We meticulously analyze the organoid field from eight distinctive vantage points, harnessing our rich experience in academic research, industrial application, and clinical practice. We present a deep exploration of the advances in organoid technology, underpinned by our long-standing involvement in this arena. Our narrative traverses the historical genesis of organoids and their transformative impact across various biomedical sectors, including oncology, toxicology, and drug development. We delve into the synergy between organoids and avant-garde technologies such as synthetic biology and single-cell omics and discuss their pivotal role in tailoring personalized medicine, enhancing high-throughput drug screening, and constructing physiologically pertinent disease models. Our comprehensive analysis and reflective discourse provide a deep dive into the existing landscape and emerging trends in organoid technology. We spotlight technological innovations, methodological evolution, and the broadening spectrum of applications, emphasizing the revolutionary influence of organoids in personalized medicine, oncology, drug discovery, and other fields. Looking ahead, we cautiously anticipate future developments in the field of organoid research, especially its potential implications for personalized patient care, new avenues of drug discovery, and clinical research. We trust that our comprehensive review will be an asset for researchers, clinicians, and patients with keen interest in personalized medical strategies. We offer a broad view of the present and prospective capabilities of organoid technology, encompassing a wide range of current and future applications. In summary, in this review we attempt a comprehensive exploration of the organoid field. We offer reflections, summaries, and projections that might be useful for current researchers and clinicians, and we hope to contribute to shaping the evolving trajectory of this dynamic and rapidly advancing field.

The alcohol extraction of P. sibiricum has exhibited significant inhibitory effects on the production of free radicals and the proliferation of non-small-cell lung carcinoma (NSCLC) A549 cells. Despite the diverse components found in alcohol extraction of P. sibiricum and its multiple targets, the active components and associated targets remain largely unidentified. Hence, there is a need for additional investigation into the pharmacodynamic elements and mechanisms of action. This study aimed to analyze and identify the components responsible for the anti-tumor activity of alcohol extraction from P. sibiricum using UPLC-Q-TOF-MS/MS for the first time. Subsequently, the targets of the active components were predicted using the SwissTargetPrediction database, whereas the targets for NSCLC were sourced from the Online Mendelian Inheritance in Man database (OMIM) and the GeneCards database. Next, the targets of chemical composition were integrated with disease targets via Venny online. GO and KEGG pathway enrichment analyses were performed utilizing DAVID. Subsequently, a network analysis of “components-targets-pathways” was established using Cytoscape 3.8.2 and assessed with the “network analyzer” plug-in. Molecular docking was conducted utilizing Autodock 1.5.6. The study aimed to examine the anti-proliferative impacts and underlying mechanisms of alcohol extraction from P. sibiricum on NSCLC through in vivo and in vitro investigations utilizing an animal model of transplanted tumor, CCK8 assay, cell scratch test, RT-qPCR, and western blotting. The study unveiled that 17 active components extracted from P. sibiricum alcohol demonstrated anti-non-small cell lung cancer (NSCLC) effects through the modulation of 191 targets and various significant signaling pathways. These pathways include Endocrine resistance, PI3K/AKT, Chemical carcinogenesis-receptor activation, Proteoglycans in cancer, EGFR tyrosine kinase inhibitor resistance, AMPK signaling pathway, and other related signaling pathways. Network analysis and molecular docking results indicated that specific compounds such as (25S)-26-O-(β-d-glucopyranosyl)-furost-5-en3β,22α,26-triol3-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-(1→4)-β-d-glucopyranoside, Timosaponin H1, Deapi-platycodin D3, (3R)-5,7-dihydroxy-6,8-dimethyl-3-(4′-hydroxybenzyl)-chroman-4-one, Disporopsin, Funkioside F, Kingianoside E, Parisyunnanoside H, and Sibiricoside B primarily targeted 17 key proteins (BCL2, EGFR, ESR1, ESR2, GRB2, IGF1R, JUN, MAP2K1, MAPK14, MAPK8, MDM2, MMP9, mTOR, PIK3CA, RAF1, RPS6KB1, and SRC) collectively. In conclusion, the alcohol extraction of P. sibiricum demonstrated inhibitory effects on cell proliferation, induction of apoptosis, and inhibition of metastasis through various pathways.

Background Consumer wearable devices such as wristbands and smartwatches have potential application value in communicable disease surveillance. Objective We investigated the ability of wearable devices to monitor COVID-19 patients of varying severity. Methods COVID-19 patients with mobile phones supporting wearable device applications were selected from Dalian Sixth People Hospital. Physiological parameters from the wearable devices and electronic questionnaires were collected from the device wearing until 14 days post-discharge. Clinical information during hospitalization was also recorded. Based on imaging data, the patients were categorized into the milder group without pneumonia and the more severe group with pneumonia. We plotted the curves of the physiological parameters of the two groups to compare the differences and changes. Results Ninety-eight patients were included in the analysis. The mean age was 39.6 ± 10.5 years, including 45 males (45.9%). There were 24 asymptomatic patients, 10 mild patients, 60 moderate patients, and 4 severe patients. Compared with the milder group, the more severe group had higher heart rate-related parameters, while the heart rate variability (HRV) was the opposite. In the more severe group, the heart rate-related parameters showed a downward trend from 0 to 7 days after the fever resolution. Among them, the resting heart rate and sleep heart rate decreased on the 25th day after the onset and were close to the milder group 1 week after discharge. Conclusions Consumer wearable devices have the potential to monitor respiratory infections. Heart rate-related parameters obtained from these devices can be sensitive indicators of COVID-19 severity and correlate with disease evolution. Trial registration ClinicalTrials.gov NCT04459637.

Fungal infections are of major concern all over the globe, and fluconazole is the most prevalently used drug to treat it. The goal of this research work was to formulate a fluconazole-embedded transfersomal gel for the treatment of fungal infections. A compatibility study between fluconazole and soya lecithin was performed by differential scanning calorimetry (DSC). Transfersomes were formulated by a thin-film hydration technique using soya lecithin and Span 80. A central composite design was adopted to prepare different formulations. Soya lecithin and Span 80 were chosen as independent variables, and the effect of these variables was studied on in vitro drug diffusion. Formulations were evaluated for entrapment efficiency and in vitro drug diffusion. The results of in vitro drug diffusion were analyzed using the analysis of variance (ANOVA) test. Optimized formulation was prepared based on the overlay plot and evaluated by scanning electron microscopy, DSC, vesicle size, polydispersity index (PDI), zeta potential, and in vitro drug diffusion studies. An optimized formulation was loaded into xanthan gum gel base and evaluated for pH, viscosity, in vitro and ex vivo drug diffusion, and antifungal activity. DSC studies revealed compatibility between fluconazole and soya lecithin. Entrapment efficiency and in vitro drug diffusion of various formulations ranged between 89.92% ± 0.20% to 97.28% ± 0.42% and 64% ± 1.56% to 85% ± 2.05%, respectively. A positive correlation was observed between in vitro drug diffusion and Span 80; conversely, a negative correlation was noted with soya lecithin. Entrapment efficiency, particle size, zeta potential, PDI, and drug diffusion of optimized formulation were 95.0% ± 2.2%, 397 ± 2 nm, −38 ± 5 mV, 0.43%, and 81 % ± 2%, respectively. SEM images showed well-distributed spherical-shaped transfersomes. In vitro, ex vivo drug diffusion and antifungal studies were conclusive of better diffusion and enhanced antifungal potential fluconazole in transfersomal formulation.

For high-precision navigation, obtaining and maintaining high-precision point-of-interest (POI) data on the road network is crucial. In urban areas with complex terrains, the accuracy of traditional road network POI acquisition methods often falls short. To address this issue, we introduce DualNet-PoiD, a hybrid neural network designed for the efficient recognition of road network POIs in intricate urban environments. This method leverages multimodal sensory data, incorporating both vehicle trajectories and remote sensing imagery. Through an enhanced dual-attention dilated link network (DAD-LinkNet) based on ResNet18, the system extracts static geometric features of roads from remote sensing images. Concurrently, an improved gated recirculation unit (GRU) captures dynamic traffic characteristics implied by vehicle trajectories. The integration of a fully connected layer (FC) enables the high-precision identification of various POIs, including traffic light intersections, gas stations, parking lots, and tunnels. To validate the efficacy of DualNet-PoiD, we collected 500 remote sensing images and 50,000 taxi trajectory data samples covering road POIs in the central urban area of the mountainous city of Chongqing. Through comprehensive area comparison experiments, DualNet-PoiD demonstrated a high recognition accuracy of 91.30%, performing robustly even under conditions of complex occlusion. This confirms the network’s capability to significantly improve POI detection in challenging urban settings.

Grasslands have been increasingly impacted by human activities, gradually becoming one of the most threatened ecosystems globally. Advanced geographic information technology and remote sensing techniques allow for a fresh perspective on studying the response of the grassland degradation index (GDI) to climate change. This study utilized remote sensing image data of grasslands to calculate the vegetation coverage and derive the GDI for five grassland regions of China from 2001 to 2019. The results indicate that the national degradation status of grasslands remained at a level of mild degradation. The increasing trend of the GDI in some regions was effectively inhibited by regional climate change, especially in the Northeastern and Northern Plain–Mountain–Hill Grassland regions, where the GDI showed a continuous decreasing trend. GDI was strongly correlated with atmospheric pressure, precipitation, temperature, and wind speed. In the arid northern region, the increasing precipitation and decreasing temperatures predominantly contributed to the depressed GDI. In the Qinghai–Tibetan Plateau Grassland region, the instability of the GDI is attributed to fluctuating atmospheric pressure, with a correlation coefficient ranging from 0.5 to 0.8. Our findings underscore the importance of meteorological factors to evaluate and forecast grassland ecosystem stability. This understanding is vital for developing informed conservation and management strategies to address current and future climate challenges.

Administrative regions are fundamental geographic elements on maps, thus making their detection in map images crucial to enhancing intelligent map interpretation. However, existing methods in this field primarily depend on the texture features within the images and do not account for the influence of spatial and co-existence relationships among different targets. In this study, taking the administrative regions of the Chinese Mainland, Taiwan, Tibet, and Henan as test targets, we employed the spatial and co-existence relationships of pairs of targets to improve target detection performance. Firstly, these four regions were detected using a simple Single-Target Cascading detection model based on RetinaNet. Subsequently, the detection results were adjusted with the spatial and co-existence relationships of each pair of targets. The adjusted outcomes demonstrate a significant increase in target detection accuracy, as well as precision (from 0.62 to 0.96) and F1 score (from 0.76 to 0.88), for the Chinese Mainland target. This study contributes to the advancement of intelligent map interpretation.

Plant community characteristics and soil properties are critical indicators for evaluating wetland degradation and restoration. In order to investigate how the degradation of inland salt marsh wetlands affects plants and soils as well as the response relationship between plants and soils under different degradation degrees, this paper selected inland salt marsh wetlands with different degradation degrees in the wetland area of western Songnen Plain, and analyzed the characteristics of plant communities, soils and their relationships. The results show that: that the important value of Gramineae plants decreased by about 21% with increasing degradation, while the vital value of Cyperaceae and weeds increased by 10% and 9%, respectively. Plant height decreased significantly, and coverage and density showed a decreasing and then increasing trend. Overall, species diversity shows a trend of increasing and then decreasing, indicating that the structure of plant communities tends to be more straightforward and more complex with increasing degradation. Soil electrical conductivity, total organic carbon (TOC) and total nitrogen (TN) content decreased significantly with the degree of degradation from ND (non degradation) to HD (heavy degradation) by 34.08%, 19.56%, and 35.82%, respectively. Soil C:N increased from 13.13 to 17.97. Soil N:P and C:P decreased from 5.56 to 3.28 and from 71.59 to 54.02, respectively. Soil factors affecting wetland plants were inconsistent at different stages of degradation. Changes in soil nitrogen and phosphorus content were correlated with changes in wetland vegetation community structure. Therefore, exploring how wetland degradation affects plants and soils can provide a scientific basis for wetland degradation assessment and wetland restoration.

Inland salt marsh wetlands have very important ecological functions in semi-arid areas. However, degradation and soil desertification have impacted these areas, making it necessary to study the impact of wetland restoration years on the soil quality of salt marsh wetland. We used remote sensing methods, field surveys, and inquiries to examine the seasonal profile effects of two-, four-, and six-year restoration periods on total nitrogen (TN), total phosphorus (TP) and the ratio of nitrogen to phosphorus (N:P) in P. australis and S. triqueter wetland natural states. Our results showed that soil TN in P. australis wetland in restored conditions was higher than that in natural conditions. The average soil TP of the S. triqueter wetlands at 0–10 cm, 10–20 cm, 20–30 cm, and 30–40 cm layers was 0.36 g/kg, 0.31 g/kg, 0.21 g/kg, and 0.17 g/kg s in September, respectively. The soil TP of the S. triqueter wetland increased slightly over the entire growing season. The restoration years had a great influence on the soil TP of the S. triqueter wetland from May to July. The soil TN in the P. australis wetland was almost restored to its natural condition in each layer during the six-year restoration period. The soil TP of the S. triqueter wetland was higher in the restored two-year period and showed a decreasing trend with an increased soil depth. Our conclusions can significantly guide the restoration of inland salt marsh wetlands.

To address the ecological security issues in the Songnen Plain, this study constructs the ecological security pattern by using the Multi-Criteria Evaluation Method, Minimum Cumulative Resistance (MCR) model, and Circuit Connectivity Model. Results show that: 1) The ecological source areas were 66, 52, and 56 blocks in 2000, 2010, and 2020 respectively, which are composed mainly of forests, water bodies, and wetlands. The distribution of resistance values of the ecological resistance surface shows a gradually increases trend from the source areas to the outward surrounding regions. The high and low value areas are more dispersed, consisting with the overall spatial distribution; 2) The numbers of ecological corridors show a temporal declining trend from 178 in 2000 to 159 in 2020 with a reduction of 645.46 km in total length. Node areas are mainly distributed in the southwestern and central-eastern regions and its number decreased from 232 in 2000 to 229 in 2020. The sizes of obstacle areas are 74029.52 km2, 70203.72 km2, and 75529.72 km2 in the three periods; 3) The size of important ecological source areas has decreased by 5779.16 km2, the area of medium ecological source areas has increased by 11466.44 km2, and the area of general ecological source areas has increased by 9509.16 km2. The areas being classified as ecological conservation, ecological enhancement, ecological restoration, and ecological control are 30346.68 km2, 8480.56 km2, 51473.92 km2, and 122047.48 km2, respectively. The multiple spatial pattern optimization strategies are proposed based on the identified ecological source areas, corridors, node points, and other comprehensive ecological security patterns. It not only provides practical reference for the ecological restoration and ecological protection in the Songnen Plain, but also can be used for the ecological security pattern investigations in other study regions in the world.