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Abstract Soil extractable nitrate, ammonium, and organic nitrogen (N) are essential N sources supporting primary productivity and regulating species composition of terrestrial plants. However, it remains unclear how plants utilize these N sources and how surface-earth environments regulate plant N utilization. Here, we establish a framework to analyze observational data of natural N isotopes in plants and soils globally, we quantify fractional contributions of soil nitrate (f NO3-), ammonium (f NH4+), and organic N (f EON) to plant-used N in soils. We find that mean annual temperature (MAT), not mean annual precipitation or atmospheric N deposition, regulates global variations of f NO3-, f NH4+, and f EON. The f NO3- increases with MAT, reaching 46% at 28.5 °C. The f NH4+ also increases with MAT, achieving a maximum of 46% at 14.4 °C, showing a decline as temperatures further increase. Meanwhile, the f EON gradually decreases with MAT, stabilizing at about 20% when the MAT exceeds 15 °C. These results clarify global plant N-use patterns and reveal temperature rather than human N loading as a key regulator, which should be considered in evaluating influences of global changes on terrestrial ecosystems.

Abstract Sciatic nerve injury (SNI) is a common type of peripheral nerve injury typically resulting from trauma, such as contusion, sharp force injuries, drug injections, pelvic fractures, or hip dislocations. It leads to both sensory and motor dysfunctions, characterized by pain, numbness, loss of sensation, muscle atrophy, reduced muscle tone, and limb paralysis. These symptoms can significantly diminish a patient’s quality of life. Following SNI, Wallerian degeneration occurs, which activates various signaling pathways, inflammatory factors, and epigenetic regulators. Despite the availability of several surgical and nonsurgical treatments, their effectiveness remains suboptimal. Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm, originating from the endoplasmic reticulum. They play a crucial role in facilitating intercellular communication and have emerged as highly promising vehicles for drug delivery. Increasing evidence supports the significant potential of exosomes in repairing SNI. This review delves into the pathological progression of SNI, techniques for generating exosomes, the molecular mechanisms behind SNI recovery with exosomes, the effectiveness of combining exosomes with other approaches for SNI repair, and the changes and future outlook for utilizing exosomes in SNI recovery.

Abstract Climate changes are known to have been a key regulator of the biodiversity in Earth's history. However, the dry‐humid degrees and alternating patterns throughout the Phanerozoic remain largely unconstrained. In this study, we report high contents (2.4 ± 3.8 mg N kg−1) and 17O anomalies (11.0 ± 7.4‰) of nitrate (NO3−) in the early Cambrian black shale from South China, likely caused by atmospheric NO3− intrusion under dry climates that followed tectonic uplift. By developing new methods to quantify aridity indices (AI, 0.06 ± 0.08) in combination with observational data with paleoclimate models, we reconstructed the historical AI variations. Our analyses revealed three significant dry‐to‐humid transitions which include Cambrian‐Ordovician to Silurian‐Permian, Permian‐Triassic boundary to middle Triassic‐early Jurassic, and Jurassic‐Paleogene to Neogene. This study quantitatively unlocked the Phanerozoic climate changes in South China, offering important evidence for understanding the co‐evolution of ecological and climatic systems in Earth's history.

Objective: To establish a predictive modeling for the risk of bloodstream infection associated with peripherally inserted central catheter (PICC). Methods: Patients receiving PICC treatment in Shenzhen People's Hospital from June 2020 to December 2020 were retrospectively enrolled and divided into the infection group and the non-infection group according to the presence and absence of PICC-related infections. Then, relevant clinical information of patients was collected and the predictors of PICC-related infection were screened by the least absolute shrinkage and selection operator regression (LASSO) model. Besides, multivariate logistic regression was used to analyze the influencing factors of PICC-related infection, A nomogram was constructed based on the results of the multivariate analysis. Ultimately, a receiver operating characteristic (ROC) curve was plotted to analyze the application value of influencing factors to predict PICC-related infections. Results: A total of 505 patients were included, including 75 patients with PICC-related infections (14.85%). The main pathogen was gram-positive cocci. The predictors screened by LASSO included age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Multivariate logistic regression analysis showed that independent risk factors of infections related to PICC included age >60 years [odds ratio (OR) = 1.722; 95% confidence interval (CI) = 1.312–3.579; P = 0.006], catheter movement (OR = 1.313; 95% CI = 1.119–3.240; P = 0.014), catheter maintenance cycle >7 days (OR = 2.199; 95% CI = 1.677–4.653; P = 0.000), direct insertion (OR = 1.036; 95% CI = 1.019–2.743; P = 0.000), poor immune function (OR = 2.322; 95% CI = 2.012–4.579; P = 0.000), complications (OR = 1.611; 95% CI = 1.133–3.454; P = 0.019), and body temperature ≥37.2 °C before PICC placement (OR = 1.713; 95% CI = 1.172–3.654; P = 0.012). Besides, the area under the ROC curve was 0.889. Conclusion: PICC-related infections are associated with factors such as age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Additionally, the LASSO model is moderately predictive for predicting the occurrence of PICC-related infections.

Abstract Background Subarachnoid hemorrhage (SAH) causes significant long-term neurocognitive dysfunction, which is associated with hippocampal neuroinflammation. Growing evidences have shown that astrocytes played a significant role in mediating neuroinflammation. Recently, in vivo reprogramming of astrocytes to neurons by NeuroD1 or PTBP1 administration has generated a lot of interests and controversies. While the debates centered on the source of neurogenesis, no attention has been paid to the changes of the astrocytes-mediated neuroinflammation and its impact on endogenous neurogenesis after NeuroD1 administration. Methods 80 adult male C57BL/6 mice were used in this study. SAH was established by pre-chiasmatic injection of 100 μl blood. AAV–NeuroD1–GFP virus was injected to the hippocampus 3 day post-SAH. Neurocognitive function, brain water content, in vivo electrophysiology, Golgi staining, western blot and immunofluorescent staining were assessed at day 14 post-virus injection. Results NeuroD1 administration markedly attenuated reactive astrocytes-mediated neuroinflammation by reversing neurotoxic A1 astrocytes transformation, decreasing the secretion of neuroinflammatory cytokines, and reducing the activation of harmful microglia. NeuroD1 treatment significantly reversed the brain–blood barrier impairment and promoted the release of neurotrophic factors pleiotrophin (PTN), all of which contributed to the improvement of cellular microenvironment and made it more suitable for neurogenesis. Interestingly, besides neurogenesis in the hippocampus from cells transfected with NeuroD1 at the early phase of SAH, NeuroD1 administration significantly boosted the endogenous neurogenesis at the late phase of SAH, which likely benefited from the improvement of the neuroinflammatory microenvironment. Functionally, NeuroD1 treatment significantly alleviated neurocognitive dysfunction impaired by SAH. Conclusions NeuroD1 significantly promoted neurofunctional recovery by attenuating reactive astrocytes-mediated neuroinflammation and boosting neurogenesis decimated by SAH. Specifically, NeuroD1 efficiently converted transfected cells, most likely astrocytes, to neurons at the early phase of SAH, suppressed astrocytes-mediated neuroinflammation and boosted endogenous neurogenesis at the late phase of SAH.

By integrating nitrogen isotope systematics of ammonia emissions and transformations in the atmosphere, this study quantified the combustion-related ammonia emission and uncovered its importance for mitigating strategies of ammonia pollution.

As a serious and elusive syndrome caused by infection, sepsis causes a high rate of mortality around the world. Our investigation aims at exploring the role and possible mechanism of specificity protein-1 (SP1) in the development of sepsis. A mouse model of sepsis was established by cecal ligation perforation, and a cellular model was stimulated by lipopolysaccharide (LPS), followed by determination of the SP1 expression. It was determined that SP1 was poorly expressed in the intestinal tissues of septic mice and LPS-treated cells. Next, we examined the interactions among SP1, histone deacetylase 4 (HDAC4), and high mobility group box 1 (HMGB1) and found that SP1 bound to the HDAC4 promoter to upregulate its expression, thereby promoting the deacetylation of HMGB1. Meanwhile, gain- or loss-of-function approaches were applied to evaluate the intestinal barrier dysfunction, oxidative stress, and inflammatory response. Overexpression of SP1 or underexpression of HMGB1 was observed to reduce intestinal barrier dysfunction, oxidative stress, and inflammatory injury. Collectively, these experimental data provide evidence reporting that SP1 could promote the HDAC4-mediated HMGB1 deacetylation to reduce intestinal barrier dysfunction, oxidative stress, and inflammatory response induced by sepsis, providing a novel therapeutic target for sepsis prevention and treatment.

Sixteen Reduced Triaxial Compression (RTC) triaxial tests were conducted to investigate the reinforcement effect of fibered clay in this paper. Palm fiber with four different fiber lengths (5 mm, 10 mm, 15 mm, and 20 mm) and four different fiber contents (0.3%, 0.5%, 0.7%, and 0.9% in mass) were utilized. Accordingly, three additional groups of triaxial tests were performed to analyze the stress path effects with four different stress paths, including RTC, Conventional Triaxial Compression (CTC), Reduced Triaxial Extension (RTE), and isotropic Triaxial Compression (TC). Three samples were tested, including fibered clay with a fiber length of 10 mm and a fiber content of 0.7% (referred to as 10 mm 0.7%), fibered clay with a fiber length of 20 mm and a fiber content of 0.5% (referred to as 20 mm 0.5%), and bare clay, which was used to reveal the fiber reinforcement of clay. All samples were tested under consolidated undrained conditions. The test results showed that in RTC conditions, the deviator stress increased to a greater extent with 0.3% mass content of fibers according to the same higher confining pressures of bare clay. Fibers primarily increased the cohesion of fibered clay, a shear strength parameter, in terms of total stress, whereas they also increased the friction angle of fibered clay in terms of effective stress. For short fibers, the coefficient of strength reinforcement of the fibered clay increased with fiber content. However, for long fibers, this reinforcement may lead to a weakening of the clay’s strength, as the long fibers may cluster or weaken along their longitude. Among the four stress paths (CTC, TC, RTC, and RTE) examined, the reinforcement took effort mainly in the CTC condition. In contrast, in unloading conditions, the fibers had little contribution to reinforcement. Consequently, in unloading conditions, such as deep excavating and slope cutting, the stress path should be considered to obtain a reliable parameter for geotechnical engineering applications.

Abstract Background Sepsis is a troublesome syndrome that can cause intestinal injury and even high mortality rates. Omega-3 fatty acids (FAs) are known to protect against intestinal damage. Accordingly, the current study set out to explore if omega-3 FAs could affect sepsis-induced intestinal injury with the involvement of the microRNA (miR)-1-3p/Notch3-Smad axis. Methods First, cecal ligation and perforation (CLP) was performed to establish septic mouse models in C57BL/6J mice, and mouse intestinal epithelial MODE-K cells were induced by lipopolysaccharide (LPS) to establish sepsis cell models. The CLP-induced septic mice or LPS-exposed cells were subjected to treatment with Omega-3 FAs and activin (Smad signaling activator), miR-1-3p inhibitor and over-expressed/short hairpin RNA (oe-/sh)-Notch3 to explore their roles in inflammation, intestinal oxidative stress and cell apoptosis. A dual-luciferase reporter gene assay was further performed to verify the regulatory relationship between miR-1-3p and Notch3. Results Omega-3 FAs inhibited CLP-induced intestinal injury and ameliorated LPS-induced intestinal epithelial cell injury by down-regulating miR-1-3p, as evidenced by decreased levels of tumor necrosis factor-α, interleukin-1β (IL-1β) and IL-6, in addition to diminished levels of reactive oxygen species, malondialdehyde levels and superoxide dismutase activity. Furthermore, miR-1-3p could down-regulate Notch3, which inactivated the Smad pathway. Conclusion Collectively, our findings indicated that omega-3 FAs elevate the expression of Notch3 by down-regulating miR-1-3p, and then blocking the Smad pathway to alleviate intestinal epithelial inflammation and oxidative stress injury caused by sepsis.

Objective: To investigate the therapeutic effect and influencing factors of perampanel (PER) on electrical status epilepticus during sleep (ESES).Methods: We retrospectively analyzed the clinical data of pediatric patients with focal epilepsy and ESES who were treated at the Epilepsy Center of Shengjing Hospital of China Medical University between January 2016 and March 2022. Changes in the spike wave index (SWI) after 24 weeks of PER add-on treatment were compared. Kaplan‒Meier survival analysis, the log-rank test and multivariate Cox regression analysis were performed.Results: A total of 54 pediatric patients met the inclusion criteria, including 33 males and 21 females. The mean age at the diagnosis of epilepsy was 6.41 ± 2.14 years and at ESES diagnosis was 7.58 ± 2.40 years. The mean ESES duration before add-on PER was 25.31 ± 15.12 months. The mean age of the patients at add-on PER initiation was 9.69 ± 2.12 years. The ESES resolved in 29 children after 6 months of PER add-on treatment, and the response rate was 53.7%. Univariate analysis with the log-rank test showed that the therapeutic effect of PER differed according to the age at ESES diagnosis and ESES duration before add-on PER treatment. Multivariate Cox regression analysis showed that only ESES duration before PER administration was a risk factor for PER treatment failure, and the other factors had no effect on the therapeutic effect.Conclusion: PER add-on treatment has a good therapeutic effect on ESES and can be used as an alternative to corticosteroid and benzodiazepines. The therapeutic effect of PER add-on treatment was not related to the dose. A longer ESES duration results in a worse therapeutic effect. Therefore, more aggressive treatment measures should be implemented for ESES.

BackgroundTalaromyces marneffei (T. marneffei) is an opportunistic fungal pathogen commonly found in human immunodeficiency virus (HIV) patients that often infects lymph nodes. Knowledge about the computed tomography (CT) characteristics of T. marneffei lymphadenopathy in HIV patients is limited. The aim of this study was to investigate the clinical and CT characteristics of T. marneffei lymphadenopathy to improve its diagnosis and promote recognition of this type of infection in radiology.MethodsBetween February 2019 and June 2021, we retrospectively reviewed the clinical features and CT characteristics of T. marneffei lymphadenopathy in 21 HIV patients.ResultsThe clinical symptoms of T. marneffei infection are non-specific. Anemia (100%), fever (85.7%) and cough and sputum production (76.2%) were the most frequent symptoms. Multiple lymphadenopathies, mainly in the mediastinum (76.2%) and mesentery (82.4%), can be fused (14.3%) and necrotic (52.4%), with slight (41.7%) and moderate enhancement (58.3%) that is heterogeneous. In addition to involving the lymph nodes, the lesions involved the lungs (81.0%), liver and spleen (42.9%), and small intestine (14.3%).ConclusionsT. marneffei is prone to affecting lymph nodes and extranodal organs in HIV patients. Although the clinical manifestations of T. marneffei infection are not specific, the possibility of T. marneffei infection should be considered if CT findings indicate multiple lesion sites.

This study investigates in the importance of non-fossil fuel NOx emissions in the surface-earth-nitrogen cycle. The study shows how changes of regional human activities directly influence δ15N signatures of deposited NOx to terrestrial environments and that emissions have largely been underestimated.

Abstract Background This study aims to evaluate specific risk factors influencing prognosis of HIV-infected patients with toxoplasma encephalitis (TE) in order to develop a prognostic risk scoring system for them. Methods This is a six-center retrospective study of hospitalized HIV/TE patients. Data including six-week mortality after diagnosis, baseline characteristics, clinical features, laboratory tests and radiological characteristics of eligible patients were assimilated for risk model establishing. Results In this study, the six-week mortality among 94 retrospective cases was 11.7% (11/94). Seven specific risk factors, viz. time from symptom onset to presentation, fever, dizziness, CD4+ T-cell counts, memory deficits, patchy brain lesions, and disorders of consciousness were calculated to be statistically associated with mortality. A criterion value of ‘9’ was selected as the optimal cut-off value of the established model. The AUC of the ROC curve of this scoring model was 0.976 (p

Introduction Acute kidney injury (AKI) is one of the most common organ dysfunction in sepsis, and increases the risk of unfavourable outcomes. Renal replacement therapy (RRT) is the predominant treatment for sepsis-associated AKI (SAKI). However, to date, no prospective randomised study has adequately addressed whether initiating RRT earlier will attenuate renal injury and improve the outcome of sepsis. The objective of the trial is to compare the early strategy with delayed strategy on the outcomes in patients with SAKI in the intensive care unit (ICU).Methods and analysis This is a large-scale, multicentre, randomised controlled trial about SAKI. In total, 460 patients with sepsis and evidence of AKI stage 2 of Kidney Disease Improving Global Outcomes (KDIGO) will be recruited and equally randomised into the early group and the delay group in a ratio of 1:1. In the early group, continuous RRT (CRRT) will be started immediately after randomisation. In the delay group, CRRT will initiated if at least one of the following criteria was met: stage 3 of KDIGO, severe hyperkalaemia, pulmonary oedema, blood urea nitrogen level higher than 112 mg/dL after randomisation. The primary outcome is overall survival in a 90-day follow-up period (90-day all-cause mortality). Other end points include 28-day, 60-day and 1-year mortality, recovery rate of renal function by day 28 and day 90, ICU and hospital length of stay, the numbers of CRRT-free days, mechanical ventilation-free days and vasopressor-free days, the rate of complications potentially related to CRRT, CRRT-related cost, and concentrations of inflammatory mediators in serum.Ethics and dissemination The trial has been approved by the Clinical Research and Application Institutional Review Board of the Second Affiliated Hospital of Guangzhou Medical University (2017–31-ks-01). Participants will be screened and enrolled from patients in the ICU with SAKI by clinicians, with no public advertisement for recruitment. Results will be disseminated in research journals and through conference presentations.Trial registration NCT03175328.

Background: The outbreak of the novel coronavirus disease (COVID-19) that began in December 2019 has posed a great threat to human health and caused a significant loss of life. In Shenzhen, 465 patients were confirmed to have COVID-19 as of August 31, 2020. In the present study, we aimed to describe the clinical characteristics of COVID-19 patients in Shenzhen and identify risk factors for the development of viral sepsis.Methods: In this retrospective study, patients who were confirmed to have a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and were admitted to the Third People's Hospital of Shenzhen from January 11 to April 27, 2020 were included in the cohort. Clinical data were extracted and followed up to May 10, 2020, by using predesigned data collection forms.Results: A total of 422 hospitalized COVID-19 patients were enrolled in this study, including 97 (23%) patients with viral sepsis at hospital admission and 325 (77%) non-septic patients. Patients with sepsis were much older than those without sepsis (57 vs. 43 years, P < 0.001) and presented with more comorbidities. Septic patients showed multiple organ dysfunction and significant abnormalities in immune- and inflammation-related biomarkers, and had poorer outcomes when compared to those without sepsis. Increased levels of interleukin-6, blood urea nitrogen, and creatine kinase were associated with the development of SARS-CoV-2-induced sepsis, and an elevated production of interleukin-6 was found to be an independent risk factor for the progression to critical illness among septic COVID-19 patients.Conclusions: SARS-CoV-2 infection-induced sepsis is critically involved in the severity and prognosis of COVID-19 patients by characterizing both aberrant immune response and uncontrolled inflammation. The development of sepsis might contribute to multiple organ dysfunction and poor outcomes in COVID-19 patients during hospitalization.

PurposeWe aimed to identify and verify the key genes and lncRNAs associated with acute lung injury (ALI) and explore the pathogenesis of ALI. Research showed that lower expression of the lncRNA metastasis-associated lung carcinoma transcript 1 (MALAT1) alleviates lung injury induced by lipopolysaccharide (LPS). Nevertheless, the mechanisms of MALAT1 on cellular apoptosis remain unclear in LPS-stimulated ALI. We investigated the mechanism of MALAT1 in modulating the apoptosis of LPS-induced human pulmonary alveolar epithelial cells (HPAEpiC).MethodsDifferentially expressed lncRNAs between the ALI samples and normal controls were identified using gene expression profiles. ALI-related genes were determined by the overlap of differentially expressed genes (DEGs), genes correlated with lung, genes correlated with key lncRNAs, and genes sharing significantly high proportions of microRNA targets with MALAT1. Quantitative real-time PCR (qPCR) was applied to detect the expression of MALAT1, microRNA (miR)-194-5p, and forkhead box P2 (FOXP2) mRNA in 1 μg/ml LPS-treated HPAEpiC. MALAT1 knockdown vectors, miR-194-5p inhibitors, and ov-FOXP2 were constructed and used to transfect HPAEpiC. The influence of MALAT1 knockdown on LPS-induced HPAEpiC proliferation and apoptosis via the miR-194-5p/FOXP2 axis was determined using Cell counting kit-8 (CCK-8) assay, flow cytometry, and Western blotting analysis, respectively. The interactions between MALAT1, miR-194-5p, and FOXP2 were verified using dual-luciferase reporter gene assay.ResultsWe identified a key lncRNA (MALAT1) and three key genes (EYA1, WNT5A, and FOXP2) that are closely correlated with the pathogenesis of ALI. LPS stimulation promoted MALAT1 expression and apoptosis and also inhibited HPAEpiC viability. MALAT1 knockdown significantly improved viability and suppressed the apoptosis of LPS-stimulated HPAEpiC. Moreover, MALAT1 directly targeted miR-194-5p, a downregulated miRNA in LPS-stimulated HPAEpiC, when FOXP2 was overexpressed. MALAT1 knockdown led to the overexpression of miR-194-5p and restrained FOXP2 expression. Furthermore, inhibition of miR-194-5p exerted a rescue effect on MALAT1 knockdown of FOXP2, whereas the overexpression of FOXP2 reversed the effect of MALAT1 knockdown on viability and apoptosis of LPS-stimulated HPAEpiC.ConclusionOur results demonstrated that MALAT1 knockdown alleviated HPAEpiC apoptosis by competitively binding to miR-194-5p and then elevating the inhibitory effect on its target FOXP2. These data provide a novel insight into the role of MALAT1 in the progression of ALI and potential diagnostic and therapeutic strategies for ALI patients.

AIM: To evaluate the long-term clinical efficacy of Shotfile software for the myopia patients with presbyopia. METHODS: A total of 43 cases(82 eyes)over the age of 35 myopia patients were treated with laser corneal surgery in our hospital, added Shotfile software at the same time, and followed up for 3a. The uncorrected visual acuity(the distance and near vision), diopter change and visual satisfaction rate were observed at 1, 2 and 3a after operation. RESULTS: At 1a after operation, there were 81 eyes(99%)with the uncorrected distance visual acuity reached the preoperative best corrected visual acuity, and 75 eyes(91%)with the uncorrected near visual acuity above 0.66, the average value of the spherical equivalent was(-0.64±0.63)D, the overall satisfaction rate was 91%. At 2a after operation, there were 79 eyes(96%)with the uncorrected distance visual acuity reached the preoperative best corrected visual acuity, and 69 eyes(84%)with the uncorrected near visual acuity above 0.66, the average value of the spherical equivalent was(-0.62±0.59)D, the overall satisfaction rate was 86%. At 3a after operation, There were 77 eyes(94%)with the uncorrected distance visual acuity reached the preoperative best corrected visual acuity, and 62 eyes(76%)with the uncorrected near visual acuity above 0.66, the average value of the spherical equivalent was(-0.55±0.56)D, the overall satisfaction rate was 81%. Intraoperative or postoperative serious complications were not found in all the cases, 1 eye of spherical equivalent with -10.0D was found -1.75D back after 1a, respected the willingness of patient for the second correction. CONCLUSION: Shotfile software for the patients myopia with presbyopia is safe and stable in the long-term clinical treatment, and the patient satisfaction is higher, but the near visual ability of some patients may be weakened with the prolongation of time, preoperative communication with patients should be fully.

AIM: To compare the visual quality between patients with moderate or high myopia and myopic astigmatism(SE -3.00～-9.00D)after femtosecond laser small incision lenticule extraction(SMILE)and laser in situ keratomileusis(LASIK). METHODS: The prospective study was applied.Eighty four patients(168 eyes)were divided into two groups: 42 patients(84 eyes)with myopia underwent SMILE was group Ⅰ, 42 patients(84 eyes)with myopia underwent LASIK was groupⅡ. The myopia degree of the patients was -3.00～-8.00D and astigmatism was -0.25～-2.00D before treatments and they were followed for 6mo. Uncorrected visual acuity(UCVA), spherical equivalent(SE), high order aberration(HOA), contrast sensitivity(CS)were compared and statistically analyzed at preoperatively, 1,3 and 6mo postoperatively. RESULTS: All operations were successful without serious complications that damaged vision. The UCVA in group Ⅰwas higher than that in group Ⅱ, and the SE was lower than that in group Ⅱ postoperatively(PPPPCONCLUSION: Moderate or high myopia and astigmatism can be effectively corrected by SMILE. Better visual acuity, more stable refractive state, less increase on SA, the recovery of CS and the improvement on visual quality, are the advantage of SMILE, but investigation with larger sample size and long term observation are needed.

Nitrogen isotope (δ15N) has been employed to differentiate major sources of atmospheric N. However, it remains a challenge to quantify contributions of multiple sources based on δ15N values of the N mixture in atmospheric samples. This study measured δ15N of bulk N in PM2.5 at an urban site of Beijing during a severe haze episode of 22–30 January 2013 and a background site of Qinghai, north-western China from 6 September to 15 October 2013, then applied a Bayesian isotope mixing model (SIAR, Stable Isotope Analysis in R) to analyse the N sources. At Beijing site, δ15N values of PM2.5 (−4.1‰ to +13.5‰, +2.8 ± 6.4‰) were distributed within the range of major anthropogenic sources (including NH3 and NO2 from coal combustion, vehicle exhausts and domestic wastes/sewage). At Menyuan site, δ15N values of PM2.5 (+8.0‰ to +27.9‰, +18.5 ± 5.8‰) were significantly higher than that of potential sources (including NH3 and NO2 from biomass burning, animal wastes, soil N cycle, fertilizer application and dust N). High molar ratios of $ {\text{NH}}_4^{+} $ to $ {\text{NO}}_3^{-} $ and/or $ {\text{SO}}_4^{2-} $ in PM2.5 at the background site suggested that the equilibrium of NH3 ↔ $ {\text{NH}}_4^{+} $ caused apparent 15N enrichments in ammonium. Results of the SIAR model showed that 39 and 32% of bulk N in PM2.5 of Beijing site were contributed from N emissions of coal combustion and vehicle exhausts, respectively, whereas N in PM2.5 at Menyuan site was derived mainly from N emissions of biomass burning (46%) and NH3 volatilization (34%). These results revealed that the stoichiometry between NH3 and acidic gases plays an important role in controlling the bulk δ15N signatures of PM2.5 and emissions of reactive N from coal combustion and urban transportation should be strictly controlled to advert the risk of haze episodes in Beijing.

Acupuncture and moxibustion have played a positive role in the postoperative rehabilitation of colon cancer, especially in the recovery of gastrointestinal function. In this paper, the current situation of the postoperative gastrointestinal function recovery of colon cancer treated by acupuncture and moxibustion was reviewed, from the following three aspects, including pathogenesis study, acute mechanism of acupuncture and moxibustion, and clinical therapeutic methods of gastrointestinal dysfunction after colon cancer surgery. The mechanism of acupuncture and moxibustion on postoperative gastrointestinal function recovery of is mainly to regulate neural pathways, improve inflammatory response, regulate gastrointestinal hormones, improve intestinal motility, increase intestinal blood flow, etc., through the interaction of neuro-endocrineimmune systems. In traditional Chinese medicine (TCM), it is considered that pathogenesis of this disease is about spleen-stomach weakness, qi stagnation and blood stasis. The main pathogenic factors of this disease include deficiency, blood stasis, dampness, and heat pathogen. In acupuncture and moxibustion treatment, it should select acupoints according to pattern differentiation, and treat the root and branch simultaneously. The common clinical therapeutic methods include acupuncture, electro-acupuncture, moxibustion, auricular acupoint sticking and pressing method, acupoint injection, acupoint sticking method, and so on. These therapeutic methods have got remarkable curative effect, and provided basis for the selection of rehabilitation plan after colon cancer surgery in clinic. [ABSTRACT FROM AUTHOR]

The dynamics of nitrate (NO3-), a major nitrogen (N) source for natural plants, has been studied mostly through experimental N addition, enzymatic assay, isotope labeling, and genetic expression. However, artificial N supply may not reasonably reflect the N strategies in natural plants because NO3- uptake and reduction may vary with external N availability. Abrupt application and short operation times, field N addition, and isotopic labeling hinder the elucidation of in situ NO3--use mechanisms. The concentration and natural isotopes of tissue NO3- can offer insights into the plant NO3- sources and dynamics in a natural context. Furthermore, they facilitate the exploration of plant NO3- utilization and its interaction with N pollution and ecosystem N cycles without disturbing the N pools. The present study was conducted to review the application of the denitrifier method for concentration and isotope analyses of NO3- in plants. Moreover, this study highlights the utility and benefits of these parameters in interpreting NO3- sources and dynamics in natural plants. We summarize the major sources and reduction processes of NO3- in plants, and discuss the implications of NO3- concentration in plant tissues based on existing data. Particular emphasis was laid on the regulation of soil NO3 - and plant ecophysiological functions in interspecific and intra-plant NO3- variations. We introduce N and O isotope systematics of NO3- in plants and discusse the principles and feasibilities of using isotopic enrichment and fractionation factors; the correlation between concentration and isotopes (N and O isotopes: δ18O and ∆17O); and isotope mass-balance calculations to constrain sources and reduction of NO3- in possible scenarios for natural plants are deliberated. Finally, we construct a preliminary framework of intraplant δ18O-NO3- variation, and summarize the uncertainties in using tissue NO3- parameters to interpret plant NO3- utilization.

Soil nitrogen (N) transformations between labile N forms (extractable organic N [EON], ammonium [NH4+], and nitrate [NO3-]) regulate soil N availability. However, it has long been difficult to quantify the transformations of total soil organic and labile N forms in soils, which has left large uncertainties in evaluating atmospheric N deposition effects on soil N dynamics. Based on concentrations and natural abundances of N isotopes of soil organic N, EON, NH4+, and NO3- across 11 forests with variant N deposition levels, we established a quantitative isotopic framework to estimate the fractions of soil N depolymerization (fD), mineralization (fM), nitrification (fN), and of NO3- losses (fL) via denitrification and leaching. Based on the fractions, the gross production and storage of corresponding soil labile N were estimated for forests of China and Japan. We found that fD, fM, and fN increased, while fL decreased with the increase of N deposition among the study forests. And the contribution of denitrification (relative to the NO3- leaching) to total NO3- losses also increased with increasing N deposition. Our method provides new and straightforward insights into the present soil N transformations and allows to evaluate the soil N status. These findings are useful for modeling forest N cycles under different N deposition regimes. [ABSTRACT FROM AUTHOR]

BACKGROUND: The study aims to illustrate the clinical characteristics and development of septic shock in intensive care unit (ICU) patients confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and to perform a comprehensive analysis of the association between septic shock and clinical outcomes in critically ill patients with coronavirus disease (COVID-19). METHODS: Patients confirmed with SARS-CoV-2 infection, who were admitted to the ICU of the Third People's Hospital of Shenzhen from January 1 to February 7, 2020, were enrolled. Clinical characteristics and outcomes were compared between patients with and without septic shock. RESULTS: In this study, 35 critically ill patients with COVID-19 were included. Among them, the median age was 64 years (interquartile range [IQR] 59-67 years), and 10 (28.4%) patients were female. The median ICU length of stay was 16 days (IQR 8-23 days). Three (8.6%) patients died during hospitalization. Nine (25.7%) patients developed septic shock in the ICU, and these patients had a significantly higher incidence of organ dysfunction and a worse prognosis than patients without septic shock. CONCLUSIONS: Septic shock is associated with a poor outcome in critically ill COVID-19 patients and is one of the hallmarks of the severity of patients receiving ICU care. A dysregulated immune response, uncontrolled inflammation, and coagulation disorders are strongly associated with the development and progression of COVID-19-related septic shock. [ABSTRACT FROM AUTHOR]

Plant nitrogen (N) use is a key component of the N cycle in terrestrial ecosystems. The supply of N to plants affects community species composition and ecosystem processes such as photosynthesis and carbon (C) accumulation. However, the availabilities and relative importance of different N forms to plants are not well understood. While nitrate (NO3-) is a major N form used by plants worldwide, it is discounted as a N source for Arctic tundra plants because of extremely low NO3- concentrations in Arctic tundra soils, undetectable soil nitrification, and plant-tissue NO3- that is typically below detection limits. Here we reexamine NO3- use by tundra plants using a sensitive denitrifier method to analyze plant-tissue NO3-. Soil-derived NO3- was detected in tundra plant tissues, and tundra plants took up soil NO3- at comparable rates to plants from relatively NO3--rich ecosystems in other biomes. Nitrate assimilation determined by 15N enrichments of leaf NO3- relative to soil NO3- accounted for 4 to 52% (as estimated by a Bayesian isotope-mixing model) of species-specific total leaf N of Alaskan tundra plants. Our finding that in situ soil NO3- availability for tundra plants is high has important implications for Arctic ecosystems, not only in determining species compositions, but also in determining the loss of N from soils via leaching and denitrification. Plant N uptake and soil N losses can strongly influence C uptake and accumulation in tundra soils. Accordingly, this evidence of NO3- availability in tundra soils is crucial for predicting C storage in tundra. [ABSTRACT FROM AUTHOR]

Using isotope mixing model (IsoSource) and natural δ15N method, this study evaluated contributions of major sources to N of PM2.5 at Beijing (collected during a severe haze episode of January 22nd-30th, 2013) and a background site (Menyuan, Qinghai province; collected from September to October of 2013) of China. At Beijing, δ15N values of PM2.5 (-4.1 - +13.5 ‰; mean = +2.8 ± 6.4 ‰) distributed within the range reported for major anthropogenic sources (including NH3 and NO2 from coal combustion, vehicle exhausts and domestic wastes/sewage). However, δ15N values of PM2.5 at the background site (+8.0 - +27.9 ‰; mean = +18.5 ± 5.8 ‰) were significantly higher than that of potential sources (including NH3 and NO2 from biomass burning, animal wastes, soil N cycle, fertilizer application, and organic N of soil dust). Evidences from molecular ratios of NH4+ to NO3- and/or SO42- in PM2.5, NH3 to NO2 and/or SO2 in ambient atmosphere suggested that the equilibrium of NH3 ↔ NH4+ caused apparent 15N enrichment only in NH4+ of PM2.5 at the background site due to more abundant NH3 than SO2 and NO2. Therefore, a net 15N enrichment (33 ‰) was assumed for NH3 sources of background PM2.5 when fractional contributions were estimated by IsoSource model. Results showed that 41 %, 30 % and 14 % of N in PM2.5 of Beijing originated from coal combustion, vehicle exhausts and domestic wastes/sewage, respectively. Background PM2.5 derived N mainly from biomass burning (58 %), animal wastes (15 %) and fertilizer application (9 %). These results revealed the regulation of the stoichiometry between ammonia and acidic gases on δ15N signals in PM2.5. Emissions of NO2 from coal combustion and NH3 from urban transportation should be strictly controlled to advert the risk of haze episodes in Beijing. [ABSTRACT FROM AUTHOR]

Moss N isotope (δ15Nbulk) has been used to monitor N deposition, but it remains questionable whether inhibition of nitrate reductase activity (NRA) by reduced dissolved N (RDN) engenders overestimation of RDN in deposition when using moss δ15Nbulk. We tested this question by investigation of δ15Nbulk and δ15Nbulk- in mosses under the dominance of RDN in N depositions of Guiyang, SW China. The δ15Nbulk of mosses on bare rock (-7.9‰) was unable to integrate total dissolved N (TDN) (δ15N = -6.3‰), but it reflected δ15N-RDN (-7.5‰) exactly. Moreover, δ15N-NO3- in mosses (-1.7‰) resembled that of wet deposition (-1.9‰). These isotopic approximations, together with low isotopic enrichment with moss [NO3-] variations, suggest the inhibition of moss NRA by RDN. Moreover, isotopic mixing modeling indicated a negligible contribution from NO3- to moss δ15Nbulk when the RDN/NO3- reaches 3.8, at which maximum overestimation (21%) of RDN in N deposition can be generated using moss δ15Nbulk as δ15N-TDN. Moss δ15N-NO3- can indicate atmospheric NO3- under distinctly high RDN/NO3- in deposition, although moss δ15Nbulk can reflect only the RDN therein. These results reveal pitfalls and new mechanisms associated with moss isotope monitoring of N deposition and underscore the importance of biotic N dynamics in biomonitoring studies. [ABSTRACT FROM AUTHOR]

Coordinated regulation of endothelial cell migration is an integral process during angiogenesis. However, molecular mechanisms regulating endothelial cell migration remain largely unknown. Increased expression of cell adhesion molecules has been implicated during angiogenesis, yet the precise role of these molecules is unclear. Here, we examined the hypothesis that intercellular adhesion molecule-1 (ICAM-1) is important for endothelial cell migration. Total cell displacement and directional migration were significantly attenuated in ICAM-l-deficient endothelium. Closer examination of ICAM-l-deficient cells revealed decreased Akt Thr308 and endothelial nitric-oxide synthase Ser1177 phosphorylation and NO bioavailability, increased actin stress fiber formation, and a lack of distinct cell polarity compared with wild-type endothelium. Supplementation of ICAM-1 mutant cells with the NO donor DETA NONOate (0.1 μM) corrected the migration defect, diminished stress fiber formation, and enhanced pseudopod and uropod formation. These data demonstrate that ICAM-1 facilitates the development of cell polarity and modulates endothelial cell migration through a pathway regulating endothelial nitric-oxide synthase activation and organization of the actin cytoskeleton. [ABSTRACT FROM AUTHOR]

Presents a study on the development of a modular approach to synthesis of cell-permeable peptides. Methodology used in the study; Production of a nonpeptide thiazolidino linkage between the modules; Combination of two membrane-permeable sequences (MPSs); General scheme for peptide ligation via thiazolidine ring formation using unprotected peptides; Discussion on the results of the study.

Stimulation of macrophages with lipopolysaccharide (LPS) leads to the production of cytokines that elicit massive liver apoptosis. We investigated the in vivo role of stress-responsive transcription factors (SRTFs) in this process focusing on the precipitating events that are sensitive to a cell-permeant peptide inhibitor of SRTF nuclear import (cSN50). In the absence of cSN50, mice challenged with LPS displayed very early bursts of inflammatory cytokines/chemokines, tumor necrosis factor α (1 h), interleukin 6 (2 h), interleukin 1 β (2 h), and monocyte chemoattractant protein 1 (2 h). Activation of both initiator caspases 8 and 9 and effector caspase 3 was noted 4 h later when full-blown DNA fragmentation and chromatin condensation were first observed (6 h). At this time an increase of pro-apoptotic Bax gene expression was observed. It was preceded by a decrease of anti-apoptotic Bcl2 and BclXL gene transcripts. Massive apoptosis was accompanied by microvascular injury manifested by hemorrhagic necrosis and a precipitous drop in blood platelets observed at 6 h. An increase in fibrinogen/fibrin degradation products and a rise in plasminogen activator inhibitor 1 occurred between 4 and 6 h. Inhibition of SRTFs nuclear import with the cSN50 peptide abrogated all these changes and increased survival from 7 to 71%. Thus, the nuclear import of SRTFs induced by LPS is a prerequisite for activation of the genetic program that governs cytokines/ chemokines production, liver apoptosis, microvascular injury, and death. These results should facilitate the rational design of drugs that protect the liver from inflammation-driven apoptosis. [ABSTRACT FROM AUTHOR]

Targeting of peptides, proteins, and other functional cargo into living cells is contingent upon efficient transport across the plasma membrane barrier. We have harnessed the signal sequence hydrophobic region (SSHR) to deliver functional cargoes to cultured cells and to experimental animals. We now report evidence that two chirally distinct forms of SSHR composed of all L or all D amino acids showed similar membrane.translocating activity as assessed by confocal microscopy, flow cytometry, and direct fluorescence measurement. An attached nuclear localization sequence ferried by the SSHR enantiomers displayed similar intracellular function by inhibiting inducible nuclear import of transcription factor nuclear factor κ B and suppressing nuclear factor κ B-dependent gene expression of cytokines. A nuclear localization sequence comprised of a positively charged cluster of amino acids was rapidly translocated by SSHR enantiomers to the interior of unilamellar phospholipid vesicles. These findings indicate that the SSHR translocates functional peptides directly through the plasma membrane phospholipid bilayer without involving chirally specific receptor/transporter mechanisms. This mechanism of SSHR translocation is suitable for facile delivery of biologically active peptides for cell-based and animal-based functional proteomic studies. [ABSTRACT FROM AUTHOR]