Nanoparticles for the treatment of spinal cord injury.

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia.

With an increase in global aging, the number of people affected by cerebrovascular diseases is also increasing, and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate. However, few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients. Similarly in Alzheimer's disease and other neurological disorders, synaptic dysfunction is recognized as the main reason for cognitive decline. Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system. Recently, nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia. This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction, neuroinflammation, oxidative stress, and blood-brain barrier dysfunction that underlie the progress of vascular dementia. Additionally, we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

First Report of Botryosphaeria dothidea Causing Leaf Blight on Parrotia subaequalis in China.

Parrotia subaequalis is of great ornamental value due to its unique bark, featuring interesting textures and colors, and its large, striking galls. These characteristics make it a popular choice for bonsai cultivation. (Yan et al. 2022) . In July 2023, an outbreak of leaf blight was observed on 40, six-month-old P. subaequalis seedlings in Anqing, Anhui, China, with an incidence rate of 80%. In the early stages of infection, small brown spots appear on the leaf surface, which gradually become round or irregular and darken to a deep brown color. As the disease progresses, the affected areas expand from the leaf margins towards the center, causing the leaf surface to become concave, wilt, and necrotize. This resulted in restricted plant growth, and in severe cases, partial or complete plant death. For isolation, 30 tissue slices (5 × 5 mm) were taken from the leaves of 10 symptomatic seedlings and surface sterilized with 75% ethanol for 5 seconds, followed by five rinses with sterilized distilled water. After two days of dark incubation at 28°C, hyphal tips of fungi were transferred onto new potato dextrose agar (PDA) plates and incubated until conidia production. Six unidentified isolates with similar morphological characteristics were obtained. The colonies, initially white, darken to black after 7 to 10 days of incubation. They produced colorless, aseptate conidia that were oblong or fusiform, measuring 18-26 µm in length and 5-8 µm in width (n=50). The morphological characteristics of the isolates resembled those of Botryosphaeria (Udayanga et al. 2015) . Isolate IS2116-1 was further confirmed through molecular methods. The rDNA internal transcribed spacer (ITS) region, translation elongation factor 1-α (TEF1-α), and beta-tubulin (TUB2) genes were amplified and sequenced using the primers ITS1/ITS4 (White et al., 1990), EF1-728F/EF1-986R, and Bt2a/Bt2b (Ferreira et al., 2021; Carbone et al., 1999), respectively. BLAST analysis revealed that the ITS (OR958722) sequence was 100% similar to the B. dothidea isolate HZ5(MH329650.1), TEF1-a (PP214058) sequence was 100% similar to the B. dothidea strain JZB310220(ON890458.1), and strain TUB2 (PP214057) sequence was 99.78% similar to the B. dothidea strain L14 (KR260833.1). Maximum likelihood analyses were performed for the combined ITS、TUB2、TEF datasets using PhyloSuite v1.2.2, the resulting phylogenetic tree indicated that isolate IS2116-1 clustered together with Botryosphaeria dothidea in a clade with 97% bootstrap support(Zheng et al. 2020) . Pathogenicity tests were conducted on 3-6 month-old P. subaequalis seedlings (n = 5) grown in a greenhouse. A conidial suspension (106 spores/ml) collected from the isolates was sprayed onto P. subaequalis seedlings, while the control was treated with distilled water. All plants were maintained in a growth chamber at 28°C with a 12-h photoperiod. The experiment was conducted twice independently . After 20 days of inoculation, brownish lesions similar to those observed in the field appeared on the treated plants, while the noninoculated control plants remained symptomless. The pathogen was reisolated from the leaves of the obviously diseased seedlings and confirmed as B. dothidea through morphological and sequence analysis. No isolates were obtained from uninoculated control plants, thus fulfilling Koch's hypothesis. This report marks the first record of B. dothidea causing leaf blight in P. subaequalis. In light of the rarity of natural P. subaequalis populations, it is imperative to assess both the extent of disease spread and its economic impact. These insights are crucial for devising strategies to protect this endangered species from disease threats and to preserve its ecological significance.

The hemostatic activity and Mechanistic roles of glucosyloxybenzyl 2-isobutylmalate extract (BSCE) from Bletilla striata (Thunb.) Rchb.f. in Inhibiting pulmonary hemorrhage.

Background: Hemorrhagic events cause numerous deaths annually worldwide, highlighting the urgent need for effective hemostatic drugs. The glucosyloxybenzyl 2-isobutylmalates Control Extract (BSCE) from the orchid plant Bletilla striata (Thunb.) Rchb.f. has demonstrated significant hemostatic activity in both in vitro and in vivo studies. However, the effect and mechanism of BSCE on non-traumatic bleeding remain unclear. Methods: Pulmonary hemorrhage was induced in 40 Sprague-Dawley rats by administering Zingiber officinale Roscoe. for 14 days. These rats were then randomly divided into five groups: model (Mod), positive control (YNBY), and BSCE low, medium, and high-dose groups. An additional 8 rats served as the control group (Con). The BSCE groups received different doses of BSCE for 10 days, while the YNBY group received Yunnan Baiyao suspension. The effects on body weight, food and water intake, red blood cell count (RBC), hemoglobin concentration (HGB), lung tissue pathology, platelet count, coagulation parameters, and fibrinolytic system markers were evaluated. Network pharmacology and molecular docking analyses were also conducted to identify potential targets and pathways involved in BSCE's effects. Results: BSCE treatment significantly improved body weight, food intake, and water consumption in rats with pulmonary hemorrhage. RBC and HGB levels increased significantly in the BSCE medium and high-dose groups compared to the Mod group (P < 0.05). Pathological examination revealed that BSCE reduced lung tissue hemorrhage and inflammation, with improvements in alveolar structure. BSCE also positively affected platelet count, thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (FIB) levels, and fibrinolytic markers (D-dimer, PAI-1, and t-PA). Network pharmacology and molecular docking identified key targets such as MMPs, CASPs, and pathways including IL-17 and TNF signaling, suggesting BSCE's involvement in hemostasis and anti-inflammatory processes. Conclusions: BSCE exhibits significant hemostatic and protective effects on Z.officinale-induced pulmonary hemorrhage in rats by improving hematological parameters, reducing lung tissue damage, and modulating the coagulation and fibrinolytic systems. The study provides evidence supporting the potential of BSCE as a therapeutic agent for hemorrhagic diseases, with its efficacy linked to multi-target and multi-pathway interactions.

Oral Bacterial Lysate OM-85: Advances in Pharmacology and Therapeutics.

Background: Bacterial lysates are known for having immunomodulatory properties and have been used mainly for the prevention and treatment of respiratory tract infections (RTIs). However, rigorous studies are needed to confirm the clinical efficacy of bacterial lysates with various bacterial antigen components, preparation methods, administration routes and course of treatment. OM-85, an oral standardized lysate prepared by alkaline lysis of 21 strains from 8 species of common respiratory tract pathogens, is indicated as immunotherapy for prevention of recurrent RTIs and acute infectious exacerbations of chronic bronchitis. OM-85 acts on multiple innate and adaptive immune targets and can restore type 1 helper T (Th1)/Th2 balance. Sporadic studies have shown advances in pharmacology and therapeutics of OM-85, and thus an update review is necessary. Methods: Literature was retrieved by searching PubMed, Web of science, Embase, CNKI, and Full Text Database of Chinese Medical Journals. Results: New roles of OM-85 were discovered in prevention and treatment of lung cancer, pulmonary tuberculosis, SARS-CoV-2 infection, allergic rhinitis, pulmonary fibrosis, atopic dermatitis, and nephrotic syndrome. Pharmacoeconomic values of OM-85 were demonstrated in prophylaxis and treatment of RTIs, chronic obstructive pulmonary disease, asthma, chronic bronchitis, rhinosinusitis and allergic rhinitis. Two consecutive courses of OM-85 (6 or 12 months apart) could prevent recurrent RTIs in children. Maternal OM-85 treatment could offer benefits for offspring. Product-specific response was observed. The efficacy of OM-85 may be associated with patient's characteristics (eg, severity of the disease, age, immune response pattern, malignancy risk stratification). Conclusion: OM-85 can improve effectiveness of standard care for some primary diseases, and carry significant pharmacoeconomic implications. The benefits shown by OM-85 in vitro and in vivo, when extrapolated to humans, are exciting but also require caution. Individualized treatment may need to be considered. It is necessary to compare the efficacy and safety of various bacterial lysate preparations.

Characteristic volatile product analysis of moldy cigar wrapper and filler using gas chromatography-ion mobility spectrometry.

Monitoring the changes of food products with easily applicable technique is important for the quality control of the products. Cigar wrapper and filler easily get moldy due to the existence of the native bacterial in the material and the moisture storage/production condition. Herein, we investigate the volatile compounds produced during the culture of tobacco using chromatography-ion mobility spectrometry (GC-IMS). 114 and 112 volatile compounds are determined with GC-IMS for the cultured cigar wrapper and cigar filler, respectively. Detailed fingerprint analysis and principal component analysis identify a series of compounds that can be used for the evaluation of the degree of mold development on cigar wrapper/filler. The results reported in this work may provide useful information for the quality evaluation of food products.

Cryotherapy for Rehabilitation After Total Knee Arthroplasty: A Comprehensive Systematic Review and Meta-Analysis.

OBJECTIVE: Despite being well-studied and widely utilized, the efficacy of cryotherapy after total knee arthroplasty (TKA) in enhancing early rehabilitation lacks consensus. The aim of this systematic review and meta-analysis was to investigate (1) whether cryotherapy is able to promote the rehabilitation of patients undergoing TKA and (2) whether continuous cold flow device has superior results than cold pack in cryotherapy. METHODS: A comprehensive trial searching was performed in the PubMed, Embase, Cochrane Library, and Google Scholar electronic databases in May, 2024. Randomized controlled trials (RCTs) comparing cryotherapy with no cryotherapy or comparing continuous cold flow device with cold pack after TKA were included. The primary outcome was visual analogue scale (VAS) of pain, and secondary outcomes included opioid consumption, blood loss (hemoglobin decrease and drainage), range of motion (ROM), swelling, length of stay (LOS), and adverse event. RESULTS: A total of 31 RCTs were included in this meta-analysis with 18 trials comparing cryotherapy with no cryotherapy and 13 trials comparing continuous cold flow device with cold pack. Pooled results showed cryotherapy group had significantly lower VAS scores than no cryotherapy group on postoperative day (POD) 1 (MD, -0.59 [95% CI, -1.14 to -0.04]; p = 0.04), POD 2 (MD, -0.84 [95% CI, -1.65 to -0.03]; p = 0.04), and POD 3 (MD, -0.86 [95% CI, -1.65 to -0.07]; p = 0.03). Cryotherapy group also showed reduced opioid consumption, reduced hemoglobin loss, decreased drainage, and improved ROM after TKA. Continuous cold flow device group had comparable VAS, opioid consumption, blood loss, ROM, knee swelling, and LOS with cold pack group. CONCLUSION: Cryotherapy can effectively alleviate postoperative pain, reduce blood loss, improve ROM, and thus promote the postoperative rehabilitation for TKA patients, but the continuous cold flow device did not show better efficacy than cold packs. These findings support the routine use of cryotherapy for the rapid rehabilitation of TKA patients, and the traditional cold pack is still recommended.

Improvement of primary Sjögren's syndrome salivary gland function by Xinfeng capsule and its effect on EGR1-STAT3 signaling pathway.

OBJECTIVES: The study was aimed to investigate the effects of Xinfeng capsule (XFC) on tissue morphology, and gland function of the salivary gland (SG) in a primary Sjögren's syndrome (pSS) mouse model. METHODS: An animal model of pSS was established by inducing SG protein in C57BL/6 mice. SG tissues were collected for tissue sequencing and subsequent experiments to detect the expression of cholinergic receptor muscarinic 3(M3R), early growth response factor 1 (EGR1) and target genes in the SG before and after XFC intervention, with in vitro validation. RESULTS: Downstream targets of the EGR1 gene were predicted and analyzed using data analysis. EGR1 showed high expression and was selected for subsequent experiments. Administration of XFC significantly increased saliva production (P < 0.001) and reduced the extent of lymphatic infiltration observed in SG. Furthermore, the expression of EGR1 was increased in the model group with statistical significance in contrast with the control group but decreased after administration of XFC (P < 0.05). Data analysis predicted the downstream target of EGR1 as signal transducer and activator of transcription 3 (STAT3), which was validated in SG tissues of mice (P < .05). CONCLUSIONS: XFC demonstrated a significant improvement in the salivary secretion function of the SG in pSS mice. EGR1 can serve as a biomarker and therapeutic target for pSS.

Fingerprinting to trace sources of suspended solids in the transport of heavy metals in urban stormwater runoff.

Suspended solids are an important pollutant in urban stormwater runoff. Past studies have mainly focused on a single transport stage of pollutants, constraining source identification of suspended solids at the catchment scale. Therefore, identifying the sources of suspended solids in stormwater runoff for the formulation of effective pollution mitigation measures is an effective way to manage suspended solids pollution in receiving waters. Sediment source fingerprinting is a widely used technique to trace the sources of river sediments, which can accurately identify the source of sediment through widely used tracers. This study used six heavy metals including Cd, Cr, Ni, Cu, Zn and Pb as tracers to quantify the sources of suspended solids in stormwater runoff from urban catchments. The spatial and temporal distribution characteristics of suspended solids during stormwater transport were investigated. The study results showed that the concentration of suspended solids was the highest in road runoff and sewer flow, especially particles <44 µm. In addition, relatively large rainfall depth, high rainfall intensity and long antecedent dry periods can lead to higher concentrations of suspended solids in roof and road runoff whereas longer rainfall duration can result in more suspended solids in sewer runoff. Sediment source fingerprinting and principal component analysis confirmed that coarse (>105 µm) particles primarily originate from road deposited sediments (63.80%), while fine (<105 µm) particles primarily originate from stormwater grate sediments and soil. The outcomes derived can help to comprehensively understand the sources of suspended solids and provide guidance for the management of urban stormwater particulate pollution, as well as being a technical reference for pollutant source traceability in urban stormwater runoff.

Targeted discovery of pea protein-derived GLP-1-secreting peptides by CaSR activation-based molecular docking and their digestive stability.

Dietary proteins could stimulate Glucagon-like peptide 1 (GLP-1) secretion. However, only a few food-derived GLP-1-secreting peptides have been identified. Herein, three GLP-1-secreting peptides were identified from pea protein hydrolysate (PPH) by calcium-sensing receptor (CaSR) activation-based molecular docking. PPH-triggered GLP-1 secretion was mediated by CaSR activation. A total of 4221 peptides were sequenced from PPH through peptidomic analysis. Subsequently, three GLP-1-secreting peptides, including RFY, FEPF, and FLFK, were screened by CaSR activation-based molecular docking, and peptide-induced GLP-1 secretion were mediated by CaSR activation. More importantly, FEPF and FLFK exhibited good digestive stability. The molecular docking suggested that binding energy between peptides and CaSR was negatively correlated with their ability to stimulate GLP-1 secretion, and some binding sites in CaSR, such as Asn102 and Tyr218, play a crucial role in stimulating GLP-1 secretion. Our findings suggest that the targeted discovery of pea protein-derived GLP-1-secreting peptides through CaSR activation-based molecular docking is an effective strategy.

Therapeutic Suppression of Atherosclerotic Burden and Vulnerability via Dll4 Inhibition in Plaque Macrophages Using Dual-Targeted Liposomes.

Atherosclerosis, characterized by chronic inflammation within the arterial wall, remains a pivotal concern in cardiovascular health. We developed a dual-targeted liposomal system encapsulating Dll4-targeting siRNA, designed to selectively bind to pro-inflammatory M1 macrophages through surface conjugation with anti-F4/80 and anti-CD68 antibodies. The Dll4-targeting siRNA is then delivered to the macrophages, where it silences Dll4 expression, inhibiting Notch signaling and reducing plaque vulnerability. Emphasizing accuracy in targeting, the system demonstrates effective suppression of Dll4, a key modulator of atherosclerotic progression, and vulnerability via VSMCs phenotypic conversion and senescence. By employing liposomes for siRNA delivery, we observed enhanced stability and specificity of the siRNA. Alongside the therapeutic efficacy, our study also evaluated the safety profile and pharmacokinetics of the dual-targeted liposomal system, revealing favorable outcomes with minimal off-target effects and optimal biodistribution. The integration of RNA interference techniques with advanced nanotechnological methodologies signifies the importance of targeted delivery in this therapeutic approach. Preliminary findings suggest a potential attenuation in plaque development and vulnerability, indicating the therapeutic promise of this approach. This research emphasizes the potential of nanocarrier-mediated precision targeting combined with a reassuring safety and pharmacokinetic profile for advancing atherosclerosis therapeutic strategies.

Isolation, identification, and technological characteristics analysis of yeast strains from Pyracantha fortuneana fruits fermentation liquid.

Pyracantha fortuneana (P. fortuneana), as a medicinal and edible plant resource, is rich in nutrients. In order to screen the high quality yeast used in Firebone fruit wine, 12 strains of yeast were isolated and purified from P. fortuneana fermentation broth by traditional pure culture method. They were identified by molecular biology as Pichia kudriavzevii (P. kudriavzevii) and Saccharomyces cerevisiae (S. cerevisiae), respectively. Strain HJ-2 could grow normally at 30℃, alcohol content 15%, SO2 mass concentration 360 mg/L, pH 3.2, sucrose mass concentration 400 g/L and glucose mass concentration 250 g/L. Strain HJ-6 could grow normally at 30℃, alcohol content 3%, SO2 concentration 360 mg/L, pH 3.2, sucrose concentration 250 g/L, glucose concentration 300 g/L. Based on the technological characteristics of fruit wine, S. cerevisiae HJ-2 has the potential of brewing P. fortuneana fruit wine. P. kudriavzevii HJ-6 has a low tolerance to ethanol and is suitable for the production of fermented beverages such as low-alcohol wine or beer.

Cellular senescence: A new perspective on the suppression of periodontitis (Review).

Cellular senescence, characterized by cell cycle arrest, can result in tissue dysfunction when senescent cells persist and accumulate. Periodontitis, a chronic inflammatory condition caused by the interaction between bacteria and the immune system of the host, primarily manifests as damage to periodontal tissues. Aging and inflammation are interlinked processes that exacerbate each other. The progression of localized chronic periodontal inflammation is often accelerated in conjunction with tissue and organ aging. The presence of senescent cells and release of inflammatory cytokines, immune modulators, growth factors and proteases that are associated with the senescence­associated secretory phenotype contribute to the deterioration of periodontal tissues. The present review aimed to elucidate the mechanisms of cellular senescence and its potential impact on periodontitis, offering novel insights for modulating the inflammatory microenvironment of periodontal tissues.

Prevalence and genetic diversity of PRRSV in Sichuan province of China from 2021 to 2023: Evidence of an ongoing epidemic transition.

Porcine reproductive and respiratory syndrome (PRRS) significantly impacts the global swine industry. Sichuan province, a key pig breeding center in China, has limited data on the molecular epidemiology of PRRS Virus (PRRSV). To address this, 1618 suspected PRRSV samples were collected from 2021 to 2023, with a prevalence rate of 39.74% (643/1618). Phylogenetic analysis showed PRRSV-2 as dominant (95.65%, 615/643), with PRRSV-1 at 4.35% (28/643). PRRSV-2 strains were further classified into NADC30-like (74.18%), NADC34-like (11.98%), C-PRRSV (5.44%), and HP-PRRSV (4.04%). The significant change in the proportions of different lineages indicates genomic divergence. NADC30-like strains exhibited significant amino acid mutations in ORF5, aiding immune evasion. Recombination analysis revealed complex patterns, primarily involving NADC30-like strains. This study highlights the genomic divergence of PRRSV in Sichuan, with NADC30-like strains becoming predominant and emerging strains like NADC34-like showing potential for further spread.

Construction of ecological security pattern in Loess Plateau counties by integrating structural connectivity and functional enhancement: A case study of Ansai District, Yan'an City, Northwest China.

Ecological security pattern is an important spatial way to maintain ecological processes and ensure the stability of ecosystem functions. As the implementation of landscape planning and decision-making, it is critically needed to consider the consistency of differentiated methods and their spatial outputs in the construction of ecological security patterns and the matching and applicability of research objects. From the perspective of integration, we combined the regional topography and landscape characteristics, integrated the morphological spatial pattern analysis and the importance evaluation results of ecosystem services to identify the ecological source, and constructed the ecological security pattern of the Ansai District of Yan'an City, the main implementation area of the Grain-for-Green Project on the Loess Plateau. The results showed that the structural and functional construction methods had low consistency in the identification of spatial protection priority. The integration-oriented method could complement each other and achieve the dual goals of structural connectivity and functional improvement. There were 202 ecological sources in the study area, with a total area of 391.58 km2, accounting for 13.3% of the total area of the study area. There were 110 ecological corridors in the study area, with a total length of 599 km, which were mainly distributed around the river channel, showing a distribution pattern of 'short and narrow dense in the north and south, long and wide in the middle'. The structure-function integration method provides new insights for ecological restoration planning of land space and promotes the research of landscape pattern, process and service.

A novel prognosis evaluation indicator of patients with sepsis created by integrating six microfluidic-based neutrophil chemotactic migration parameters.

Impaired neutrophil migration in sepsis is associated with a poor prognosis. The potential of utilizing neutrophil chemotaxis to assess immune function, disease severity, and patient prognosis in sepsis remains underexplored. This study employed an innovative approach by integrating a multi-tip pipette with a Six-Unit microfluidic chip (SU6-chip) to establish gradients in six microchannels, thereby analyzing neutrophil chemotaxis in sepsis patients. We compared chemotactic parameters between healthy controls (NH = 20) and sepsis patients (NS1 = 25), observing significant differences in gradient perception time (GP), migration distance (MD), peak velocity (Vmax), chemotactic index (CI), reverse migration rate (RM), and stop migration number (SM). A novel composite indicator, the Sepsis Neutrophil Migration Evaluation (SNME) index, was developed by integrating these six chemotactic migration parameters. The SNME index and individual chemotaxis parameters showed significant correlations with the Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE II) score, hypersensitivity C-reactive protein (hs-CRP), and heparin-binding protein (HBP). Moreover, the SNME index demonstrated potential for monitoring sepsis progression, with ROC analysis confirming its predictive accuracy (area under the curve [AUC] = 0.895, cutoff value = 31.5, specificity = 86.73 %, sensitivity = 86.71 %), outperforming individual neutrophil chemotactic parameters. In conclusion, the SNME index represents a promising new tool for adjunctive diagnosis and prognosis assessment in patients with sepsis.

Evaluation of complications in patients with mandible fractures undergoing chronic kidney disease in the United States.

BACKGROUND: This research aims to assess the demographic characteristics, prevalence, outcomes, and complications in chronic kidney disease (CKD) patients following mandible fractures in the United States using a nationally representative database. METHODS: We analyzed data from the National Inpatient Sample from 2010 to 2019 in the United States. Patients with mandible fractures were categorized into three groups based on the International Classification of Diseases, Ninth and Tenth Revisions (ICD-9-CM and ICD-10-CM): end-stage renal disease (ESRD), non-ESRD CKD, and healthy kidney function. Chi-squared tests and analysis of variance (ANOVA) were used to compare these groups. Additionally, multivariate regression analysis was performed to determine whether CKD is an independent risk factor for complications in patients with mandible fractures. RESULTS: A total of 38,481 patients in the United States were estimated to have experienced mandible fractures between 2010 and 2019. The incidence rate of non-ESRD CKD in patients with mandible fractures significantly increased over time, while the prevalence of ESRD remained stable during the ten-year period. Compared to the healthy kidney function group, patients with chronic kidney disease exhibited higher hospital costs, longer hospitalization durations, and higher in-hospital mortality rates. Additionally, they had greater odds ratios for most of the investigated complications. CONCLUSIONS: This study revealed a steady annual increase in the morbidity rate of non-ESRD CKD among patients with mandible fractures, while ESRD prevalence remained stable over ten years. We observed a close association between chronic kidney disease and the prognosis of patients with mandible fractures. Clinicians should prioritize preventive measures and appropriate management of mandibular fractures in patients with CKD.

Genome-wide identification of kiwifruit K+ channel Shaker family members and their response to low-K+ stress.

BACKGROUND: 'Hongyang' kiwifruit (Actinidia chinensis cv 'Hongyang') is a high-quality variety of A. chinensis with the advantages of high yield, early ripening, and high stress tolerance. Studies have confirmed that the Shaker K+ genes family is involved in plant uptake and distribution of potassium (K+). RESULTS: Twenty-eight Shaker genes were identified and analyzed from the 'Hongyang' kiwifruit (A. chinensis cv 'Hongyang') genome. Subcellular localization results showed that more than one-third of the AcShaker genes were on the cell membrane. Phylogenetic analysis indicated that the AcShaker genes were divided into six subfamilies (I-VI). Conservative model, gene structure, and structural domain analyses showed that AcShaker genes of the same subfamily have similar sequence features and structure. The promoter cis-elements of the AcShaker genes were classified into hormone-associated cis-elements and environmentally stress-associated cis-elements. The results of chromosomal localization and duplicated gene analysis demonstrated that AcShaker genes were distributed on 18 chromosomes, and segmental duplication was the prime mode of gene duplication in the AcShaker family. GO enrichment analysis manifested that the ion-conducting pathway of the AcShaker family plays a crucial role in regulating plant growth and development and adversity stress. Compared with the transcriptome data of the control group, all AcShaker genes were expressed under low-K+stress, and the expression differences of three genes (AcShaker15, AcShaker17, and AcShaker22) were highly significant. The qRT-PCR results showed a high correlation with the transcriptome data, which indicated that these three differentially expressed genes could regulate low-K+ stress and reduce K+ damage in kiwifruit plants, thus improving the resistance to low-K+ stress. Comparison between the salt stress and control transcriptomic data revealed that the expression of AcShaker11 and AcShaker18 genes was significantly different and lower under salt stress, indicating that both genes could be involved in salt stress resistance in kiwifruit. CONCLUSION: The results showed that 28 AcShaker genes were identified and all expressed under low K+ stress, among which AcShaker22 was differentially and significantly upregulated. The AcShaker22 gene can be used as a candidate gene to cultivate new varieties of kiwifruit resistant to low K+ and provide a reference for exploring more properties and functions of the AcShaker genes.