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BackgroundPostoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) is effective in preventing the recurrence of hepatocellular carcinoma (HCC) in patients treated with surgery. However, there is a lack of reports studying the risk factors associated with recurrence in HCC patients who received PA-TACE. In this study, we identified the independent risk factors for recurrence of HCC patients who received PA-TACE. We also developed a novel, effective, and valid nomogram to predict the individual probability of recurrence, 1, 3, and 5 years after PA-TACE.MethodsA retrospective study was performed to identify the independent risk factors for recurrence of HCC in a group of 502 patients diagnosed in stage B based on the Barcelona Clinic Liver Cancer (BCLC) evaluation system for HCC that underwent curative resections. Then, subgroup analysis was performed for 184 patients who received PA-TACE, who were included in the training cohort. The other 147 HCC patients were included in a validation cohort. A recurrence-free survival (RFS)-predicting nomogram was constructed, and results were assessed using calibration and decision curves and a time-dependent AUC diagram.ResultsPA-TACE was shown to be a significant independent prognostic value for patients with BCLC stage B [p < 0.001, hazard ratio (HR) = 0.508, 95% CI = 0.375–0.689 for OS, p = 0.002; HR = 0.670, 95%CI = 0.517–0.868 for RFS]. Alpha fetoprotein (AFP), tumor number, tumor size, microvascular invasion (MVI), and differentiation were considered as independent risk factors for RFS in the training cohort, and these were further confirmed in the validation cohort. Next, a nomogram was constructed to predict RFS. The C-index for RFS in the nomogram was 0.721 (95% CI = 0.718–0.724), which was higher than SNACOR, HAP, and CHIP scores (0.587, 0.573, and 0.607, respectively). Calibration and decision curve analyses and a time-dependent AUC diagram were used. Our nomogram showed stronger performance than these other nomograms in both the training and validation cohorts.ConclusionsHCC patients diagnosed as stage B according to BCLC may benefit from PA-TACE after surgery. The RFS nomogram presented here provides an accurate and reliable prognostic model to monitor recurrence. Patients with a high recurrence score based on the nomogram should receive additional high-end imaging exams and shorter timeframes in between follow-up visits.

The aim of the paper was to observe the effect of Huang Jing Zan Yu capsule on oligoasthenozoospermia rats genetic expression profiles and sperm through microarray method. Cyclophosphamide was used to induce injury of rats testis as to form oligoasthenozoospermia model, while levocarnitine in control group. Huang Jing Zan Yu capsule was administered to treatment group for 2 weeks. Then detection system of sperm quality was used to determine indexes such as sperm density and motility. Genome-wide Oligo chips were used to analyse the changes of genetic expression profiles. The sperm amount, density, motility, and viability of Huang Jing Zan Yu capsule a level and b level had different degree improvements, and had clear differences compared with the control group (P < 0.05). Differential expression genes were scattered in eight prominent signalling pathways, which were apoptosis pathways, cellular adhesion molecule signalling pathways, neurotrophic factor signalling pathways, olfaction transduction pathways, steroid hormone biosynthesis pathways, metabolic pathways, retinol metabolism pathways and arachidonic acid metabolism pathways. Six new key genes, Adam7, Lcn5, Slc7a8, Hoxa10, Slc4a9, Vom2r57 were confirmed. Huang Jing Zan Yu capsule can improve sperm vitality of oligoasthenozoospermia rats. The mechanism is associated with eight prominent signalling pathways, which are apoptosis pathways, cellular adhesion molecule signalling pathways, neurotrophic factor signalling pathways, olfaction transduction pathways, steroid hormone biosynthesis pathways, metabolic pathways, retinol metabolism pathways and arachidonic acid metabolism pathways. [ABSTRACT FROM AUTHOR]

Accumulating evidence supports the existence of cancer stem cells (CSCs) in human tumors, and the successful certification of CSCs may lead to the identification of therapeutic targets, which are more effective for the treatment of cancer. The use of spherical cancer models has increased in popularity in cancer stem cell investigations. Tumorospheres, which are used as a model of CSCs and are established in serum-free medium supplemented with growth factors under non-adherent conditions, are one of the most commonly used cancer spherical models and are a valuable method for enriching the CSC fraction. To investigate whether this model is applicable in lung cancer (LC), the identification of lung CSCs and their capacities is essential. In the present study, lung CSCs were enriched by sphere-forming culturing and their stem-like properties were assessed. The results indicated that the lung tumorospheres had enhanced proliferation, clonality, invasion and cisplatin-resistance, and showed significantly increased expression levels of CD133 and breast cancer resistance protein (ABCG2). These results, together with findings previously reported in literature, indicated that the sphere-forming culturing of LC cells induced the enrichment of CSCs and that the tumorospheres exhibited stem cell characteristics. In addition, the higher expression levels of CD133 and ABCG2 in the tumorospheres may provide a rationale for therapeutic targets for LC. [ABSTRACT FROM AUTHOR]

Many cases of acute pain can be resolved with few side effects. However, some cases of acute pain may persist beyond the time required for tissue injury recovery and transit to chronic pain, which is hard to treat. The mechanisms underlying pain transition are not entirely understood, and treatment strategies are lacking. In this study, the hyperalgesic priming model was established on rats to study pain transition by injection of carrageenan (Car) and prostaglandin E2 (PGE2). The expression levels of protein kinase C epsilon (PKCε) and transient receptor potential vanilloid 1 (TRPV1) in the L4–L6 dorsal root ganglion (DRG) were investigated. Electroacupuncture (EA) is a form of acupuncture in which a small electric current is passed between a pair of acupuncture needles. EA was administrated, and its effect on hyperalgesia and PKCε and TRPV1 expression was investigated. The PKCε–TRPV1 signaling pathway in DRG was implicated in the pain transition. EA increased the pain threshold of model animals and regulated the high expression of PKCε and TRPV1. Moreover, EA also regulated hyperalgesia and high TRPV1 expression induced by selective PKCε activation. We also found that EA partly increased chronic pain threshold, even though it was only administered between the Car and PGE2 injections. These findings suggested that EA could prevent the transition from acute to chronic pain by inhibiting the PKCε and TRPV1 expression in the peripheral nervous system.

Abstract Background Transcutaneous electrical acupoint stimulation (TEAS), which is also known as acupuncture-like transcutaneous electrical nerve stimulation (TENS), has been widely used in acute or chronic pain. However, previous research has not demonstrated that TEAS is effective for cancer-related pain. Opioid drugs are strongly recommended for treating cancer-related pain, but opioid-induced immunosuppression is still the most intractable drug-induced medical problem. Evaluating the efficacy and potential advantage of TEAS combined with opioid drugs in moderate and severe cancer-related pain in China is important because such studies are lacking. Methods/Design This trial is a multicenter, prospective randomized controlled clinical trial. In total, 160 patients who were enrolled from two hospitals in the Zhejiang Province (China) will be randomly allocated into two groups: a TEAS group and sham TEAS group without acupoint electrical stimulation. Both groups will receive a 21-day interval of chemotherapy and conventional cancer pain therapy. Fifteen treatment sessions will be performed over a three-week period. The primary outcomes will be measured by changes in the Numerical Rating Scale (NRS) scores and equivalent dosage of morphine at baseline, three weeks of treatment and one two-week follow-up. The secondary outcome measures include cellular immunity function, life quality assessment, opioids side effects assessment, and safety and compliance evaluation. Discussion This trial is expected to clarify whether TEAS is effective for cancer-related pain. These results demonstrate the advantage of TEAS combined with opioid drugs on improving immune function and decreasing opioid induced side effects. Trial registration Chinese Clinical Trial Registry, ChiCTR-13003803. Registered on 27 August 2013.

Chronic pain is a costly health problem that impairs health-related quality of life when not effectively treated. Regulating the transition from acute to chronic pain is a new therapeutic strategy for chronic pain that presents a major clinical challenge. The underlying mechanisms of pain transition are not entirely understood, and strategies for preventing this transition are lacking. Here, a hyperalgesic priming model was used to study the potential mechanism by which γ-aminobutyric acid receptor type A (GABAAR) in the dorsal root ganglion (DRG) contributes to pain transition. Furthermore, electroacupuncture (EA), a modern method of acupuncture, was administered to regulate pain transition, and the mechanism underlying EA’s regulatory effect was investigated. Hyperalgesic priming was induced by intraplanar injection of carrageenan (Car)/prostaglandin E2 (PGE2). The decrease in mechanical withdrawal threshold (MWT) induced by PGE2 returned to baseline 4 h after injection in NS + PGE2 group, and still persisted 24 h after injection in Car + PGE2 group. Lower expression of GABAAR in the lumbar DRG was observed in the model rats. Furthermore, activating or blocking GABAAR could reversed the long-lasting hyperalgesia induced by Car/PGE2 injection or produced a persistent hyperalgesia. In addition, GABAAR may be involved in Protein Kinase C epsilon (PKCε) activation in the DRG, a mark molecular of pain transition. EA considerably increased the mechanical pain thresholds of hyperalgesic priming model mammals in both the acute and chronic phases. Furthermore, EA upregulated the expression of GABAAR and inhibited the activation of PKCε in the DRG. In addition, peripheral administration of picrotoxin blocked the analgesic effect of EA on the model rats and abolished the regulatory effect of EA on PKCε activation. These findings suggested that GABAAR plays a key role in both the transition from acute to chronic pain and the analgesic effect of EA on hyperalgesic priming.

Precipitation is the primary source of water available to vegetation. Although many studies have explored the spatially heterogeneous relationship between vegetation and precipitation, it remains unknown why different precipitation levels lead to comparable vegetation growth and the same precipitation level leads to different vegetation growth. Here we provided a simple, new parameterized calculation method to describe the precipitation-vegetation relation. The new method characterizes the ability of local precipitation to supply the water needed for vegetation growth. In the case of China, the method can explain vegetation growth better than the common indices that represent water supply, such as the SPEI, the PDSI, and soil moisture. We further explored what induces the differences in the capacity of soil to redistribute local precipitation for vegetation growth by examining the sensitivity of the residual value between actual vegetation growth and theoretical precipitation-determined vegetation growth to water storage-related soil properties. Our results indicate that soil texture and soil depth to bedrock rather than climatic factors predicted the above mentioned residual values, which implies that soil water storage capacity can increase or decrease the amount of local precipitation needed for vegetation growth. Soil physical properties that involve a high clay content and a thickness between 1 and 3 m are favorable for the stored precipitation fraction for vegetation growth. Neglecting this effect of soil water storage capacity may introduce inaccuracies when simulating the impact of future climate change on vegetation growth.

Bone cancer pain (BCP) is a clinical refractory mixed pain involving neuropathic and inflammatory pain, with the underlying mechanisms remaining largely unknown. Electro-acupuncture (EA) can partly alleviate BCP according to previous research. We aim to explore the proteins and major pathways involved in BCP and EA treatment through phosphoproteomic profiling. BCP rat model was built by tibial inoculation of MRMT-1 mammary gland carcinoma cells. Mechanical hyperalgesia determined by paw withdrawal thresholds (PWTs) and bone destruction manifested on the radiographs confirmed the success of modeling, which were attenuated by EA treatment. The differentially expressed phosphorylated proteins (DEPs) co-regulated by BCP modeling and EA treatment in rat dorsal root ganglions (DRGs) were analyzed through PEX100 Protein microarray. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DEPs were significantly enriched in mammalian target of rapamycin (mTOR) signaling pathway. The phosphorylations of mTOR at Ser2448 and Thr2446 were increased in BCP and downregulated by EA. In addition, the phosphorylation of S6K and Akt, markers of the mTOR complex, were also increased in BCP and downregulated by EA. Inhibition of mTOR signaling alleviated the PWTs of BCP rats, while the mTOR agonist impaired the analgesic effect of EA. Thus, our study provided a landscape of protein phosphorylation changes in DRGs of EA-treated BCP rats and revealed that mTOR signaling can be potentially targeted to alleviate BCP by EA treatment.

Anxiety is a common comorbidity associated with chronic pain, which results in chronic pain complexification and difficulty in treatment. Electroacupuncture (EA) is commonly used to treat chronic pain and anxiety. However, the underlying mechanisms of the EA effect are largely unknown. Here, we showed that a circuitry underlying chronic pain induces anxiety disorders, and EA can treat them by regulating such circuitry. Using chemogenetic methods, we found that chemogenetic activation of the rostral anterior cingulate cortex (rACC) glutamatergic output to the thalamus induced anxiety disorders in control rats. Then, chemogenetic inhibition of the rACC-thalamus circuitry reduced anxiety-like behavior produced by intraplantar injection of the complete Freund’s adjuvant (CFA). In this study, we examined the effects of EA on a rat model of CFA-mediated anxiety-like behaviors and the related mechanisms. We found that chemogenetic activation of the rACC-thalamus circuitry effectively blocked the effects of EA on chronic pain-induced anxiety-like behaviors in CFA rats. These results demonstrate an underlying rACC-thalamus glutamatergic circuitry that regulates CFA-mediated anxiety-like behaviors. This study also provides a potential mechanistic explanation for EA treatment of anxiety caused by chronic pain.

Background: The data on long-term outcomes of patients infected by SARS-CoV-2 and treated with extracorporeal membrane oxygenation (ECMO) in China are merely available.Methods: A retrospective study included 73 patients infected by SARS-CoV-2 and treated with ECMO in 21 intensive care units in Hubei, China. Data on demographic information, clinical features, laboratory tests, ECMO durations, complications, and living status were collected.Results: The 73 ECMO-treated patients had a median age of 62 (range 33–78) years and 42 (63.6%) were males. Before ECMO initiation, patients had severe respiratory failure on mechanical ventilation with a median PO2/FiO2 of 71.9 [interquartile range (IQR), 58.6–87.0] mmHg and a median PCO2 of 62 [IQR, 43–84] mmHg on arterial blood analyses. The median duration from symptom onset to invasive mechanical ventilation, and to ECMO initiation was19 [IQR, 15–25] days, and 23 [IQR, 19–31] days. Before and after ECMO initiation, the proportions of patients receiving prone position ventilation were 58.9 and 69.9%, respectively. The median duration of ECMO support was 18.5 [IQR 12–30] days. During the treatments with ECMO, major hemorrhages occurred in 31 (42.5%) patients, and oxygenators were replaced in 21 (28.8%) patients. Since ECMO initiation, the 30-day mortality and 60-day mortality were 63.0 and 80.8%, respectively.Conclusions: In Hubei, China, the ECMO-treated patients infected by SARS-CoV-2 were of a broad age range and with severe hypoxemia. The durations of ECMO support, accompanied with increased complications, were relatively long. The long-term mortality in these patients was considerably high.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has led to a large and increasing number of patients requiring prolonged mechanical ventilation and tracheostomy. The indication and optimal timing of tracheostomy in COVID-19 patients are still unclear, and the outcomes about tracheostomy have not been extensively reported. We aimed to describe the clinical characteristics and outcomes of patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who underwent elective tracheostomies.Methods: The multi-center, retrospective, observational study investigated all the COVID-19 patients who underwent elective tracheostomies in intensive care units (ICUs) of 23 hospitals in Hubei province, China, from January 8, 2020 to March 25, 2020. Demographic information, clinical characteristics, treatment, details of the tracheostomy procedure, successful weaning after tracheostomy, and living status were collected and analyzed. Data were compared between early tracheostomy patients (tracheostomy performed within 14 days of intubation) and late tracheostomy patients (tracheostomy performed after 14 days).Results: A total of 80 patients were included. The median duration from endotracheal intubation to tracheostomy was 17.5 [IQR 11.3–27.0] days. Most tracheotomies were performed by ICU physician [62 (77.5%)], and using percutaneous techniques [63 (78.8%)] at the ICU bedside [76 (95.0%)]. The most common complication was tracheostoma bleeding [14 (17.5%)], and major bleeding occurred in 4 (5.0%) patients. At 60 days after intubation, 31 (38.8%) patients experienced successful weaning from ventilator, 17 (21.2%) patients discharged from ICU, and 43 (53.8%) patients had died. Higher 60 day mortality [22 (73.3%) vs. 21 (42.0%)] were identified in patients who underwent early tracheostomy.Conclusions: In patients with SARS-CoV-2 pneumonia, tracheostomies were feasible to conduct by ICU physician at bedside with few major complications. Compared with tracheostomies conducted after 14 days of intubation, tracheostomies within 14 days were associated with an increased mortality rate.

Complex regional pain syndrome type-I (CRPS-I) is chronic neurological disorder accompanied with devastating pain. Most conventional medical treatments lack effectiveness, making CRPS-I a challenging clinical condition. Electroacupuncture (EA) showed effectiveness in alleviating the pain symptoms of CRPS-I patients. However, the molecular mechanisms underlying EA's therapeutic effect are still not well-understood. Here, we established the rat chronic post-ischemic pain (CPIP) model to mimic CRPS-I and performed repetitive EA on bilateral hind limbs of the CPIP model rats. We then performed RNA-sequencing (RNA-Seq) to study the differences in gene expression, gene networks, and molecular pathways in ipsilateral DRGs innervating the hind limb of the CPIP model rats with and without repetitive EA treatment. Our results found that repetitive EA treatment significantly alleviated mechanical allodynia in bilateral hind limbs of CPIP model rats. RNA-Seq analysis indicated that EA modulated the expression of multiple genes and gene networks in the DRGs of CPIP model rats. Further bioinformatics analysis identified the up-regulation of an array of genes involved in biological process such as neutrophil chemotaxis and immune response in the DRGs of CPIP model rats after EA treatment. Thus, these results suggest that EA may alleviate pain response in CPIP model rats via regulating multiple genes. Our work may help to further advance the understandings of the molecular mechanisms underlying EA's therapeutic effects on CRPS-I and help to identify novel targets for CRPS-I treatment.

Electroacupuncture (EA) can effectively modulate pain perception and pain-related negative affect; however, we do not know whether the effect of EA on sensation and affect is parallel, or dissociated, interactional. In this study, we observed the effects of the anterior cingulate cortex (ACC) lesion and the primary somatosensory cortex (S1) activation on pain perception, pain-related affection, and neural oscillation in S1. ACC lesions did not affect pain perception but relieved pain-paired aversion. S1 activation increased pain perception and anxious behavior. EA can mitigate pain perception regardless of whether there is an ACC lesion. Chronic pain may increase the delta and theta band oscillatory activity in the S1 brain region and decrease the oscillatory activity in the alpha, beta, and gamma bands. EA intervention may inhibit the oscillatory activity of the alpha and beta bands. These results suggest that EA may mitigate chronic pain by relieving pain perception and reducing pain-related affection through different mechanisms. This evidence builds upon findings from previous studies of chronic pain and EA treatment.

Exploring land use change is crucial to planning land space scientifically in a region. Taking the ecological conservation area (ECA) in western Beijing as the study area, we employ ArcGIS 10.2, landscape pattern index and multiple mathematical statistics to explore the temporal and spatial variation of land use from 2000 to 2020. Patch-generating Land Use Simulation (PLUS), Future Land Use Simulation (FLUS) and Markov models were used to simulate and predict the current land use in 2020. The models were evaluated for accuracy, and the more accurate PLUS model was selected and used to simulate and predict the potential land use in the study area in 2030 under two management scenarios. The main findings of this research are: (1) From 2000 to 2020, the construction land increased constantly, and the area of cultivated land and grassland decreased significantly. (2) For predicting the spatial distribution of land use in the study area, the PLUS model was more accurate than the FLUS model. (3) The land-use prediction of the study area in 2030 shows that the area of grassland, forest and water is approximately equal to their corresponding value in 2020, but the construction land increased constantly by occupying the surrounding cultivated land. According to this research, the continuous decrease of cultivated land in favor of increasing construction land will cause losses to the ecological service function of the ECA, which is not beneficial to the sustainable development of the region. Relevant departments should take corresponding measures to reduce this practice and promote sustainable development, particularly in the southern and western areas of the ECA where there is less construction land.

Abstract Hydroquinone (HQ) is one of the most frequently used and effective skin-lightening products to treat skin hyperpigmentation disorders, including postinflammatory hyperpigmentation, melasma and solar lentigines. HQ is also widely used in cosmetic products for skin whitening. However, HQ treatment can evoke substantial skin irritation, a side effect that remains poorly understood. Here we demonstrate that HQ is an activator of the peripheral irritant receptor transient receptor potential (TRP) cation channel member A1 (TRPA1). HQ failed to activate TRPV1, TRPV4 or TRPM8. HQ-induced TRPA1 activation was dependent on essential redox-sensitive cysteine and lysine residues within N-terminus of channel protein. HQ elicited Ca2+ influx in a subpopulation of mouse sensory neurons sensitive to the TRPA1 agonist, mustard oil. HQ-induced neuronal responses were significantly reduced by TRPA1 inhibitors, and reduced in neurons isolated from Trpa1-deficient mice. In mice, intraplantar injection of HQ at clinically relevant concentrations elicited both acute pain and persistent mechanical hyperalgesia which were almost completely abolished by TRPA1 inhibitors. These findings identify TRPA1 as a molecular target for HQ and provide insights into the mechanism of HQ-induced skin irritation. These findings also suggest that selective TRPA1 antagonists may be useful to counteract HQ-induced skin irritation.

Complex regional pain syndrome type 1 (CRPS-I) is a debilitating pain condition that significantly affects life quality of patients. It remains a clinically challenging condition and the mechanisms of CRPS-I have not been fully elucidated. Here, we investigated the involvement of TRPV1, a non-selective cation channel important for integrating various painful stimuli, in an animal model of CRPS-I. A rat model of chronic post-ischemia pain (CPIP) was established to mimic CRPS-I. TRPV1 expression was significantly increased in hind paw tissue and small to medium-sized dorsal root ganglion (DRG) neurons of CPIP rats. CPIP rats showed increased TRPV1 current density and capsaicin responding rate in small-sized nociceptive DRG neurons. Local pharmacological blockage of TRPV1 with the specific antagonist AMG9810, at a dosage that does not produce hyperthermia or affect thermal perception or locomotor activity, effectively attenuated thermal and mechanical hypersensitivity in bilateral hind paws of CPIP rats and reduced the hyperexcitability of DRG neurons induced by CPIP. CPIP rats showed bilateral spinal astrocyte and microglia activations, which were significantly attenuated by AMG9810 treatment. These findings identified an important role of TRPV1 in mediating thermal and mechanical hypersensitivity in a CRPS-I animal model and further suggest local pharmacological blocking TRPV1 may represent an effective approach to ameliorate CRPS-I.

Our previous studies have confirmed that electroacupuncture (EA) can effectively intervene in pain memory, but the neural mechanism involved remains unclear. In this study, we observed the effects of EA in regulating pain memory-related behaviors and synchronous neural oscillations in the rostral anterior cingulate cortex (rACC). During nociceptive behavioral testing, pain memory induced a nonpain stimulus that spurred a neural oscillatory reaction similar to that caused by pain stimuli in the rACC. After EA, nonpain stimuli did not induce decreased neural oscillatory activity in the rACC until the presentation of pain stimuli. During aversive behavioral testing, EA, through the downregulation of theta power, inhibited the retrieval of aversive memory and relieved pain memory-induced aversive behaviors. These changes of oscillatory activity may be the hallmarks of EA therapy for pain memory.

To meet the sustainable development goals in rocky desertified regions like Guizhou Province in China, we should maximize the crop yield with minimal environmental costs. In this study, we first calculated the yield gap for 6 main crop species in Guizhou Province and evaluated the quantitative relationships between crop yield and influencing variables utilizing ensembled artificial neural networks. We also tested the influence of adjusting the quantity of local fertilization and irrigation on crop production in Guizhou Province. Results showed that the total yield of the selected crops had, on average, reached over 72.5% of the theoretical maximum yield. Increasing irrigation tended to be more consistently effective at increasing crop yield than additional fertilization. Conversely, appropriate reduction of fertilization may even benefit crop yield in some regions, simultaneously resulting in significantly higher fertilization efficiency with lower residuals in the environment. The total positive impact of continuous intensification of irrigation and fertilization on most crop species was limited. Therefore, local stakeholders are advised to consider other agricultural management measures to improve crop yield in this region.

In this paper, cross-spectrum analysis was used to verify the agreement of periodicity between the global LAI (leaf area index) and climate factors. The results demonstrated that the LAI of deciduous forests and permanent wetlands have high agreement with temperature, rainfall and radiation over annual cycles. A low agreement between the LAI and seasonal climate variables was observed for some of the temperate and tropical vegetation types including shrublands and evergreen broadleaf forests, possibly due to the diversity of vegetation and human activities. Across all vegetation types, the LAI demonstrated a large time lag following variation in radiation (>1 month), whereas relatively short lag periods were observed between the LAI and annual temperature (around 2 weeks)/rainfall patterns (less than 10 days), suggesting that the impact of radiation on global vegetation growth is relatively slow, which is in accord with the results of previous studies. This work can provide a benchmark of the phenological drivers in global vegetation, from the perspective of periodicity, as well as helping to parameterize and refine the DGVMs (Dynamic Global Vegetation Models) for different vegetation types.

Oxidation products of the naturally occurring phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphatidylcholine (PAPC), which are known as OxPAPC, accumulate in atherosclerotic lesions and at other sites of inflammation in conditions such as septic inflammation and acute lung injury to exert pro- or anti-inflammatory effects. It is currently unknown whether OxPAPC also contributes to inflammatory pain and peripheral neuronal excitability in these conditions. Here, we observed that OxPAPC dose-dependently and selectively activated human TRPA1 nociceptive ion channels expressed in HEK293 cells in vitro, without any effect on other TRP channels, including TRPV1, TRPV4 and TRPM8. OxPAPC agonist activity was dependent on essential cysteine and lysine residues within the N-terminus of the TRPA1 channel protein. OxPAPC activated calcium influx into a subset of mouse sensory neurons which were also sensitive to the TRPA1 agonist mustard oil. Neuronal OxPAPC responses were largely abolished in neurons isolated from TRPA1-deficient mice. Intraplantar injection of OxPAPC into the mouse hind paw induced acute pain and persistent mechanical hyperalgesia and this effect was attenuated by the TRPA1 inhibitor, HC-030031. More importantly, we found levels of OxPAPC to be significantly increased in inflamed tissue in a mouse model of chronic inflammatory pain, identified by the binding of an OxPAPC-specific antibody. These findings suggest that TRPA1 is a molecular target for OxPAPC and OxPAPC may contribute to chronic inflammatory pain through TRPA1 activation. Targeting against OxPAPC and TRPA1 signaling pathway may be promising in inflammatory pain treatment.

The goal of this study is to analyze the statistics of the backscatter signal from bovine cancellous bone using a Nakagami model and to evaluate the feasibility of Nakagami-model parameters for cancellous bone characterization. Ultrasonic backscatter measurements were performed on 24 bovine cancellous bone specimens in vitro and the backscatter signals were compensated for the frequency-dependent attenuation prior to the envelope detection. The statistics of the backscatter envelope were modeled using the Nakagami distribution. Our results reveal that the backscatter envelope mainly followed pre-Rayleigh distributions, and the deviations of the backscatter envelope from Rayleigh distribution decreased with increasing bone density. The Nakagami shape parameter (i.e., m) was significantly correlated with bone densities (R=0.78–0.81, ) and trabecular microstructures (, ). The scale parameter (i.e., ) and signal-to-noise ratio (SNR) also yielded significant correlations with bone density and structural features. Multiple linear regressions showed that bone volume fraction (BV/TV) was the main predictor of the Nakagami parameters, and microstructure produced significantly independent contribution to the prediction of Nakagami distribution parameters, explaining an additional 10.2% of the variance at most. The in vitro study showed that statistical parameters derived with Nakagami model might be useful for cancellous bone characterization, and statistical analysis has potential for ultrasonic backscatter bone evaluation. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a life-threatening illness characterized by a complex pathophysiology, involving not only the respiratory system but also nonpulmonary distal organs. Although advances in the management of ARDS have led to a distinct improvement in ARDS-related mortality, ARDS is still a life-threatening respiratory condition with long-term consequences. A better understanding of the pathophysiology of this condition will allow us to create a personalized treatment strategy for improving clinical outcomes. In this article, we present a general overview p38 mitogen-activated protein kinase (p38MAPK) and recent advances in understanding its functions. We consider the potential of the pharmacological targeting of p38MAPK pathways to treat ARDS.