Mulches assist degraded soil recovery via stimulating biogeochemical cycling: metagenomic analysis.

Soil degradation of urban greening has caused soil fertility loss and soil organic carbon depletion. Organic mulches are made from natural origin materials, and represent a cost-effective and environment-friendly remediation method for urban greening. To reveal the effects of organic mulch on soil physicochemical characteristics and fertility, we selected a site that was covered with organic mulch for 6 years and a nearby lawn-covered site. The results showed that soil organic matter, total nitrogen, and available phosphorus levels were improved, especially at a depth of 0-20 cm. The activities of cellulase, invertase, and dehydrogenase in soil covered with organic mulch were 17.46%, 78.98%, and 283.19% higher than those under lawn, respectively. The marker genes of fermentation, aerobic respiration, methanogenesis, and methane oxidation were also enriched in the soil under organic mulch. Nitrogen cycling was generally repressed by the organic mulch, but the assimilatory nitrate and nitrite reduction processes were enhanced. The activity of alkaline phosphatase was 12.63% higher in the mulch-covered soil, and functional genes involved in phosphorus cycling were also enriched. This study presents a comprehensive investigation of the influence of organic mulch on soil microbes and provides a deeper insight into the recovery strategy for soil degradation following urban greening. KEY POINTS: • Long-term cover with organic mulches assists soil recovery from degradation • Soil physical and chemical properties were changed by organic mulches • Organic mulches enhanced genes involved in microbially mediated C and P cycling • Soil organic matter was derived from decomposition of organic mulch and carbon fixation • N cycling was repressed by mulches, except for assimilatory NO2- and NO3- reductions.

The Changes in the Quantity of Lymphocyte Subpopulations during the Process of Sepsis.

Sepsis remains a global challenge, especially in low- and middle-income countries, where there is an urgent need for easily accessible and cost-effective biomarkers to predict the occurrence and prognosis of sepsis. Lymphocyte counts are easy to measure clinically, and a large body of animal and clinical research has shown that lymphocyte counts are closely related to the incidence and prognosis of sepsis. This review extensively collected experimental articles related to lymphocyte counts since the unification of the definition of sepsis. The article categorizes and discusses the relationship between absolute lymphocyte counts, intrinsic lymphocyte subsets, effector T-lymphocytes, B-lymphocytes, dendritic cells, and the incidence and prognosis of sepsis. The results indicate that comparisons of absolute lymphocyte counts alone are meaningless. However, in addition to absolute lymphocyte counts, innate lymphocyte subsets, effector T-cells, B-lymphocytes, and dendritic cells have shown certain research value in related studies.

Molecular characterization of TRPA1 and its function in temperature preference in Eriocheir sinensis.

Chinese mitten crab (Eriocheir sinensis) is an economically important aquaculture species, and its growth and development are regulated by temperature, but the molecular mechanisms of the responses to temperature remain unclear. Herein, we identified TRPA1 from E. sinensis, a member of the TRP family of heat receptor potential channels, performed RACE cloning and bioinformatics analysis, and investigated the effect of TRPA1 on temperature responses and molting by real-time PCR and RNA interference (RNAi). The open reading frame of Es-TRPA1 is 3660 bp, and the encoded protein has a molecular weight of 136.91 kDa, and is expressed in embryos and juveniles. RNAi-mediated silencing decreased Es-TRPA1 expression in juvenile crabs, molting rate was decreased, mortality was increased, and crabs avoided cold areas (4 °C) much less than control juvenile crabs. The results suggest that Es-TRPA1 is involved in regulating temperature adaptation and molting processes in E. sinensis. The findings lay a foundation for further exploration of temperature regulation mechanisms in E. sinensis and other crustaceans.

Method to Solve Underwater Laser Weak Waves and Superimposed Waves.

With the rapid development of Lidar technology, the use of Lidar for underwater terrain detection has become feasible. There is still a challenge in the process of signal resolution: the underwater laser echo signal is different to propagating in the air, and it is easy to produce weak waves and superimposed waves. However, existing waveform decomposition methods are not effective in processing these waveform signals, and the underwater waveform signal cannot be correctly decomposed, resulting in subsequent data-processing errors. To address these issues, this study used a drone equipped with a 532 nm laser to detect a pond as the study background. This paper proposes an improved inflection point selection decomposition method to estimate the parameter. By comparing it with other decomposition methods, we found that the RMSE is 2.544 and R2 is 0.995975, which is more stable and accurate. After estimating the parameters, this study used oscillating particle swarm optimization (OPSO) and the Levenberg-Marquardt algorithm (LM) to optimize the estimated parameters; the final results show that the method in this paper is closer to the original waveform. In order to verify the processing effect of the method on complex waveform, this paper decomposes and optimizes the simulated complex waveforms; the final RMSE is 0.0016, R2 is 1, and the Gaussian component after decomposition can fully represent the original waveform. This method is better than other decomposition methods in complex waveform decomposition, especially regarding weak waves and superimposed waves.

Prediction of in-hospital mortality in patients with exertional heatstroke: a 13-year retrospective study.

Hyperactivity of coagulation is common in exertional heatstroke (EHS). Disseminated intravascular coagulation (DIC) is the most severe form of coagulation dysfunction and associated with poor outcome. DIC, temperature and Glasgow coma scale score were identified as independent risk factors for in-hospital mortality by multivariate logistic regression analysis, and we developed a nomogram for predicting in-hospital mortality in a 13-year EHS patient cohort. The nomogram was assessed by calibration curves and bootstrap with 1,000 resamples. The receiver operating characteristic curve was constructed, and the area under the curve (AUC) was compared. Two hundred and ten patients were included. The in-hospital mortality was 9.0%, and the incidence of DIC was 17.6%. The AUC of the nomogram was 0.897 (95% CI 0.848-0.935, p < .0001) and was non-inferior to SOFA and APACHE II scores but superior to SIRS score, which were widely-used score systems of disease severity. The nomogram contributed to the adverse outcome prediction of EHS.

Microinjection-based CRISPR/Cas9 mutagenesis in the decapoda crustaceans Neocaridina heteropoda and Eriocheir sinensis.

CRISPR/Cas9 technology has been applied to many arthropods. However, application of this technology to crustaceans remains limited because of the unique characteristics of embryos. Our group has developed a microinjection system to introduce the CRISPR/Cas9 system into Neocaridina heteropoda embryos (one-cell stage). Using the developed method, we mutated the target gene Nh-scarlet (N. heteropoda scarlet), which functions in eye development and pigmentation. The results showed that both eye color and shape were altered in individuals in which Nh-scarlet was knocked out. Furthermore, this system was also successfully applied to another decapod crustacean, Eriocheir sinensis. DNA sequencing revealed that the zoeae with red eyes had an edited version of Es-scarlet. This study provides a stable microinjection method for freshwater crustaceans, and will contribute to functional genomics studies in various decapods.

Integrating Multilevel Functional Characteristics Reveals Aberrant Neural Patterns during Audiovisual Emotional Processing in Depression.

Emotion dysregulation is one of the core features of major depressive disorder (MDD). However, most studies in depression have focused on unimodal emotion processing, whereas emotional perception in daily life is highly dependent on multimodal sensory inputs. Here, we proposed a novel multilevel discriminative framework to identify the altered neural patterns in processing audiovisual emotion in MDD. Seventy-four participants underwent an audiovisual emotional task functional magnetic resonance imaging scanning. Three levels of whole-brain functional features were extracted for each subject, including the task-evoked activation, task-modulated connectivity, combined activation and connectivity. Support vector machine classification and prediction models were built to identify MDD from controls and evaluate clinical relevance. We revealed that complex neural networks including the emotion regulation network (prefrontal areas and limbic-subcortical regions) and the multisensory integration network (lateral temporal cortex and motor areas) had the discriminative power. Moreover, by integrating comprehensive information of local and interactive processes, multilevel models could lead to a substantial increase in classification accuracy and depression severity prediction. Together, we highlight the high representational capacity of machine learning algorithms to characterize the complex network abnormalities associated with emotional regulation and multisensory integration in MDD. These findings provide novel evidence for the neural mechanisms underlying multimodal emotion dysregulation of depression.

Development of a recombinase-aided amplification assay for rapid detection of human norovirus GII.4.

BACKGROUND: Human noroviruses are one of the main causes of foodborne illnesses and represent a serious public health concern. Rapid and sensitive assays for human norovirus detection are undoubtedly necessary for clinical diagnosis, especially in regions without more sophisticated equipment. METHOD: The rapid reverse transcription recombinase-aided amplification (RT-RAA) is a fast, robust and isothermal nucleic acid detection method based on enzyme reaction. This method can complete the sample detection at 39 °C in 30 min. In this study, we successfully established a rapid reverse transcription recombinase-aided amplification (RT-RAA) assay for the detection of human norovirus GII.4 and applied this assay to clinical samples, as well as comparison with commercial reverse transcription real-time fluorescence quantitative PCR (RT-qPCR). RESULTS: At 95% probability, the detection sensitivity of RT-RAA was 3.425 log10 genomic copies (LGC)/reaction. Moreover, no cross-reaction was observed with other norovirus genogroups and other common foodborne viruses. Stool samples were examined by RT-RAA and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Compared of RT-qPCR, kappa values for human norovirus detection with RT-RAA were 0.894 (p < 0.001), indicating that both assays were in agreement. CONCLUSION: This RT-RAA assay provides a rapid, specific, and sensitive assay for human norovirus detection and is suitable for clinical testing.

Motor Circuit and Superior Temporal Sulcus Activities Linked to Individual Differences in Multisensory Speech Perception.

Integrating multimodal information into a unified perception is a fundamental human capacity. McGurk effect is a remarkable multisensory illusion that demonstrates a percept different from incongruent auditory and visual syllables. However, not all listeners perceive the McGurk illusion to the same degree. The neural basis for individual differences in modulation of multisensory integration and syllabic perception remains largely unclear. To probe the possible involvement of specific neural circuits in individual differences in multisensory speech perception, we first implemented a behavioral experiment to examine the McGurk susceptibility. Then, functional magnetic resonance imaging was performed in 63 participants to measure the brain activity in response to non-McGurk audiovisual syllables. We revealed significant individual variability in McGurk illusion perception. Moreover, we found significant differential activations of the auditory and visual regions and the left Superior temporal sulcus (STS), as well as multiple motor areas between strong and weak McGurk perceivers. Importantly, the individual engagement of the STS and motor areas could specifically predict the behavioral McGurk susceptibility, contrary to the sensory regions. These findings suggest that the distinct multimodal integration in STS as well as coordinated phonemic modulatory processes in motor circuits may serve as a neural substrate for interindividual differences in multisensory speech perception.

Single-cell transcriptome profiling reveals the mechanism of abnormal proliferation of epithelial cells in congenital cystic adenomatoid malformation.

OBJECTIVES: Congenital cystic adenomatoid malformation (CCAM) is the most common congenital pulmonary anomaly with unknown etiology. Here, single-cell RNA sequencing (scRNA-seq) was used to map its cellular landscape and identify the underlying cellular and molecular events related to CCAM. METHODS: This study involved a 4.25 year old patient with grade Ⅱ-Ⅲ CCAM at the Children's Hospital of Fudan University. Samples of lesioned and non-lesioned areas were collected during surgery for scRNA-seq. RESULTS: In total, 19,904 cells were obtained with median UMI counts of 7032 per cell and 1995 median genes per cell. In terms of lesioned and non-lesioned areas, epithelial cells accounted for 27.23% and 17.85%, respectively, while mesenchymal cells accounted for 2.67% and 16.06%, respectively (P < 0.0001). Further clustering of epithelial cells revealed that the fractions of alveolar type 1 cells (AT1, N: 23.65%; L: 49.81%), AT2(N: 2.02%; L: 5.26%), club-1(N: 9.02%; L: 17.57%), club-3(N: 1.18%; L: 4.15%), and basal cells (N: 0.34%; L: 2.93%) were increased in lesioned samples (P < 0.0001). Pseudotime trajectory analysis showed tracks of club-1/basal cells→AT2→club-3→AT1 and club-1,2/basal→AT2. Mast cells (N: 0.63%; L: 2.48%) were also increased in lesioned samples and interactions of CD44 with HBEGF and FGFR2 were detected between mast and epithelial cells. CONCLUSIONS: AT1, AT2, club, and basal cells were increased in CCAM patients, and newly defined club-1/3 and basal cells might be the origin of proliferating AT1 and AT2 cells. Increased mast cells might promote epithelial cell proliferation through interactions of CD44 with HBEGF and FGFR2.

Ultrasonic manifestations and clinical analysis of 25 uterine rupture cases.

PURPOSE: To explore the risk factors, ultrasonic manifestations, clinical features, and maternal and neonatal outcomes associated with complete uterine rupture. BASIC PROCEDURES: All cases of complete uterine rupture diagnosed and treated in Jiangxi Maternal and Child Health Hospital from January 2012 to July 2018 were retrospectively analyzed. Risk factors, ultrasonic manifestations, clinical features, and maternal and infant outcomes were analyzed. RESULT: All patients had a history of uterine surgery or induced abortion. Ultrasound examination revealed 15 cases of complete rupture of the uterus, five cases of missed diagnosis, three cases of misdiagnosis, and two cases of direct emergency operation without ultrasonography because of typical clinical manifestations and critical conditions. The clinical manifestations of 25 cases of uterine rupture varied from asymptomatic to clinical signs of "resting" rupture of the uterus to severe pain, hypotension, shock, and coma. All patients underwent surgical treatment, of which one case underwent DIC and died after rescue. The maternal mortality rate was 4% (1/25), the mortality rate of newborns (two pregnant women was twins) was 44% (12/27). CONCLUSION: A history of uterine surgery is a major risk factor for uterine rupture. Attention should be paid not only to women who are pregnant again after cesarean section but also to those who have undergone other uterine operations (such as laparoscopic myomectomy, laparoscopic cornual pregnancy removal, etc.), delivery plans should be formulated accordingly. In cases of sudden abdominal pain during pregnancy or childbirth, the possibility of uterine rupture should be considered to achieve a timely and correct diagnosis and treatment.

Altered glial glutamate transporter expression in descending circuitry and the emergence of pain chronicity.

BACKGROUND: The glutamate type 1 transporter (GLT1) plays a major role in glutamate homeostasis in the brain. Although alterations of GLT1 activity have been linked to persistent pain, the significance of these changes is poorly understood. Focusing on the rostral ventromedial medulla, a key site in pain modulation, we examined the expression and function of GLT1 and related transcription factor kappa B-motif binding phosphoprotein (KBBP) in rats after adjuvant-induced hind paw inflammation. RESULTS: After inflammation, GLT1 and KBBP showed an early upregulation and gradual transition to downregulation that lasted throughout the eight-week observation period. Nitration of GLT1 was reduced at 30 min and increased at eight weeks after inflammation, suggesting an initial increase and later decrease in transporter activity. Mechanical hyperalgesia and paw edema exhibited an initial developing phase with peak hyperalgesia at 4 to 24 h, a subsequent attenuating phase, followed by a late persistent phase that lasted for months. The downregulation of GLT1 occurred at a time when hyperalgesia transitioned into the persistent phase. In the rostral ventromedial medulla, pharmacological block with dihydrokainic acid and RNAi of GLT1 and KBBP increased nociception and overexpression of GLT1 reversed persistent hyperalgesia. Further, the initial upregulation of GLT1 and KBBP was blocked by local anesthetic block, and pretreatment with dihydrokainic acid facilitated the development of hyperalgesia. CONCLUSIONS: These results suggest that the initial increased GLT1 activity depends on injury input and serves to dampen the development of hyperalgesia. However, later downregulation of GLT1 fosters the net descending facilitation as injury persists, leading to the emergence of persistent pain.

Cortical response to categorical color perception in infants investigated by near-infrared spectroscopy.

Perceptual color space is continuous; however, we tend to divide it into only a small number of categories. It is unclear whether categorical color perception is obtained solely through the development of the visual system or whether it is affected by language acquisition. To address this issue, we recruited prelinguistic infants (5- to 7-mo-olds) to measure changes in brain activity in relation to categorical color differences by using near-infrared spectroscopy (NIRS). We presented two sets of geometric figures to infants: One set altered in color between green and blue, and the other set altered between two different shades of green. We found a significant increase in hemodynamic responses during the between-category alternations, but not during the within-category alternations. These differences in hemodynamic response based on categorical relationship were observed only in the bilateral occipitotemporal regions, and not in the occipital region. We confirmed that categorical color differences yield behavioral differences in infants. We also observed comparable hemodynamic responses to categorical color differences in adults. The present study provided the first evidence, to our knowledge, that colors of different categories are represented differently in the visual cortex of prelinguistic infants, which implies that color categories may develop independently before language acquisition.

Synthesis and application of imidazolium-based ionic liquids as extraction solvent for pretreatment of triazole fungicides in water samples.

Five novel ionic liquids (ILs), 1,3-dibutylimidazolium bromide [BBMIm][Br], 1-pentyl-3-butylimidazolium bromide [BPMIm][Br], 1-hexyl-3-butylimidazolium bromide [BHMIm][Br], 1,1'-(butane-1,4-diyl)bis(3-butylimidazolium) bromide [C4(BMIm)2][Br2], and 1,1'-(butane-1,4-diyl)bis(3-methylimidazolium) bromide [C4(MIm)2][Br2], were prepared and used in situ to react with bis(trifluoromethane)sulfonamide lithium salt to extract the myclobutanil, tebuconazole, cyproconazole, and prothioconazole from water samples. The results showed that mono-cationic ILs had much better recovery than dicationic ILs, and mono-imidazolium IL bearing butyl groups at N-1 and N-3 sites had the best recovery. When the length of the alkyl substituent group was more than four carbons at N-3 site, the recovery decreased with increase of alkyl chain length of 1-butylimidazolium IL. The extraction efficiency order of triazoles from high to low was [BBMIm][Br], [BPMIm][Br], [BHMIm][Br], [BMIm][Br] (1-butyl-3-methylimidazolium bromide), [C4(BMIm)2]Br2, [C4(MIm)2]Br2. An in situ ionic liquid dispersive liquid-liquid microextraction combined with ultrasmall superparamagnetic Fe3O4 was established as a pretreatment method for enrichment of triazole fungicides in water samples by using the synthetic [BBMIm][Br] as the cationic IL and used to detect analytes followed by high-performance liquid chromatography. Under the optimized conditions, the proposed method showed a good linearity within a range of 5-250 µg L-1, with the determination coefficient (r2) varying from 0.998 to 0.999. High mean enrichment factors were achieved ranging from 187 to 323, and the recoveries of the target analytes from real water samples at spiking levels of 10.0, 20.0, and 50.0 µg L-1 were between 70.1% and 115.0%. The limits of detection for the analytes were 0.74-1.44 µg L-1, and the intra-day relative standard deviations varied from 5.23% to 8.65%. The proposed method can be further applied to analyze and monitor pesticides in other related samples. Graphical Abstract The scheme of the in-situ DLLME method for the determination of triazoles using the imidazolium-based ionic liquids.

Further observations on the behavioral and neural effects of bone marrow stromal cells in rodent pain models.

BACKGROUND: Bone marrow stromal cells (BMSCs) have shown potential to treat chronic pain, although much still needs to be learned about their efficacy and mechanisms of action under different pain conditions. Here, we provide further convergent evidence on the effects of BMSCs in rodent pain models. RESULTS: In an orofacial pain model involving injury of a tendon of the masseter muscle, BMSCs attenuated behavioral pain conditions assessed by von Frey filaments and a conditioned place avoidance test in female Sprague-Dawley rats. The antihyperalgesia of BMSCs in females lasted for <8 weeks, which is shorter than that seen in males. To relate preclinical findings to human clinical conditions, we used human BMSCs. Human BMSCs (1.5 M cells, i.v.) attenuated mechanical and thermal hyperalgesia induced by spinal nerve ligation and suppressed spinal nerve ligation-induced aversive behavior, and the effect persisted through the 8-week observation period. In a trigeminal slice preparation, BMSC-treated and nerve-injured C57B/L mice showed reduced amplitude and frequency of spontaneous excitatory postsynaptic currents, as well as excitatory synaptic currents evoked by electrical stimulation of the trigeminal nerve root, suggesting inhibition of trigeminal neuronal hyperexcitability and primary afferent input by BMSCs. Finally, we observed that GluN2A (N-methyl-D-aspartate receptor subunit 2A) tyrosine phosphorylation and protein kinase Cgamma (PKCg) immunoreactivity in rostral ventromedial medulla was suppressed at 8 weeks after BMSC in tendon-injured rats. CONCLUSIONS: Collectively, the present work adds convergent evidence supporting the use of BMSCs in pain control. As PKCg activity related to N-methyl-D-aspartate receptor activation is critical in opioid tolerance, these results help to understand the mechanisms of BMSC-produced long-term antihyperalgesia, which requires opioid receptors in rostral ventromedial medulla and apparently lacks the development of tolerance.

Growth mechanism of Ge-doped CZTSSe thin film by sputtering method and solar cells.

Ge-doped CZTSSe thin films were obtained by covering a thin Ge layer on CZTS precursors, followed by a selenization process. The effect of the Ge layer thickness on the morphologies and structural properties of Ge-doped CZTSSe thin films were studied. It was found that Ge doping could promote grain growth to form a compact thin film. The lattice shrank in the top-half of the film due to the smaller atomic radius of Ge, leading to the formation of tensile stress. According to thermodynamic analysis, Sn was easier to be selenized than Ge. Thus, Ge preferred to remain on the surface and increased the surface roughness when the Ge layer was thin. CZTSe was easier to form than Ge-doped CZTSe, which caused difficulty in Ge doping. These results offered a theoretical and experimental guide for preparing Ge-doped CZTSSe thin films for the potential applications in low-cost solar cells. With a 10 nm Ge layer on the top of the precursor, the conversion efficiency of the solar cell improved to 5.38% with an open-circuit voltage of 403 mV, a short-circuit current density of 28.51 mA cm-2 and a fill factor of 46.83% after Ge doping.

Infants' visual system nonretinotopically integrates color signals along a motion trajectory.

Whereas early visual processing has been considered primarily retinotopic, recent studies have revealed significant contributions of nonretinotopic processing to the human perception of fundamental visual features. For adult vision, it has been shown that information about color, shape, and size is nonretinotipically integrated along the motion trajectory, which could bring about clear and unblurred perception of a moving object. Since this nonretinotopic processing presumably includes tight and elaborated cooperation among functional cortical modules for different visual attributes, how this processing matures in the course of brain development is an important unexplored question. Here we show that the nonretinotopic integration of color signals is fully developed in infants at five months of age. Using preferential looking, we found significantly better temporal segregation of colors for moving patterns than for flickering patterns, even when the retinal color alternation rate was the same. This effect could be ascribed to the integration of color signals along a motion trajectory. Furthermore, the infants' color segmentation performance was comparable to that of human adults. Given that both the motion processing and color vision of 5-month-old infants are still under development, our findings suggest that nonretinotopic color processing develops concurrently with basic color and motion processing. Our findings not only support the notion of an early presence of cross-modal interactions in the brain, but also indicate the early development of a purposive cross-module interaction for elegant visual computation.

Spinal 5-HT3 receptors mediate descending facilitation and contribute to behavioral hypersensitivity via a reciprocal neuron-glial signaling cascade.

BACKGROUND: It has been recently recognized that the descending serotonin (5-HT) system from the rostral ventromedial medulla (RVM) in the brainstem and the 5-HT3 receptor subtype in the spinal dorsal horn are involved in enhanced descending pain facilitation after tissue and nerve injury. However, the mechanisms underlying the activation of the 5-HT3 receptor and its contribution to facilitation of pain remain unclear. RESULTS: In the present study, activation of spinal 5-HT3 receptors by intrathecal injection of a selective 5-HT3 receptor agonist SR 57227 induced spinal glial hyperactivity, neuronal hyperexcitability and pain hypersensitivity in rats. We found that there was neuron-to-microglia signaling via the chemokine fractalkine, microglia to astrocyte signaling via cytokine IL-18, astrocyte to neuronal signaling by IL-1ß, and enhanced activation of NMDA receptors in the spinal dorsal horn. Glial hyperactivation in spinal dorsal horn after hindpaw inflammation was also attenuated by molecular depletion of the descending 5-HT system by intra-RVM Tph-2 shRNA interference. CONCLUSIONS: These findings offer new insights into the cellular and molecular mechanisms at the spinal level responsible for descending 5-HT-mediated pain facilitation during the development of persistent pain after tissue and nerve injury. New pain therapies should focus on prime targets of descending facilitation-induced glial involvement, and in particular the blocking of intercellular signaling transduction between neurons and glia.

Up-regulation of interleukin-23 induces persistent allodynia via CX3CL1 and interleukin-18 signaling in the rat spinal cord after tetanic sciatic stimulation.

Tetanic stimulation of the sciatic nerve (TSS) induces sciatic nerve injury and long-lasting pain hypersensitivity in rats, and spinal glial activation and proinflammatory cytokines releases are involved. In the present study, we showed that spinal interleukin (IL)-23 and its receptor, IL-23R, are crucial for the development of mechanical allodynia after TSS. In the spinal dorsal horn, both IL-23 and IL-23R are expressed in astrocytes, and this expression is substantially increased after TSS. Inhibition of IL-23 signaling attenuated TSS-induced allodynia and decreased the induction of glial fibrillary acidic protein (GFAP, an astrocytic marker). Conversely, intrathecally delivered IL-23 induced a persistent allodynia. Similar to IL-23 signaling, an increase in IL-18 and its receptor, IL-18R, as well as CX3CL1 and its receptor, CX3CR1, was simultaneously observed in the spinal dorsal horn after TSS. Interestingly, IL-18 and CX3CR1 were exclusively expressed in microglia, while IL-18R was mainly localized in astrocytes. In contrast, CX3CL1 was predominately expressed in neurons and secondarily in astrocytes. The functional inhibition of CX3CL1 and IL-18 signaling attenuated TSS-induced allodynia and suppressed IL-23 and IL-23R upregulation. Activation of CX3CR1 and IL-18R induced similar behavioral and biochemical changes to those observed after TSS. These results indicate that the interaction among CX3CL1, IL-18 and IL-23 signaling in the spinal cord plays a critical role in the development of allodynia. Thus, interrupting this chemokine-cytokine network might provide a novel therapeutic strategy for neuropathic pain.

Monocyte HLA-DR level on admission predicting in-hospital mortality rate in exertional heatstroke: A 12-year retrospective study.

BACKGROUND: Exertional heatstroke (EHS), a fatal illness, pronounces multiple organ dysfunction syndrome (MODS) and high mortality rate. Currently, no ideal factor prognoses EHS. Decreased monocyte human leukocyte-DR antigen (mHLA-DR) has been observed in critically ill individuals, particularly in those with sepsis. While most research focus on the pro-inflammatory response exploration in EHS, there are few studies related to immunosuppression, and no report targeted on mHLA-DR in EHS. The present study tried to explore the prognostic value of mHLA-DR levels in EHS patients. METHODS: This was a single-center retrospective study. Clinical data of EHS patients admitted to the intensive care unit of the General Hospital of Southern Theatre Command between January 1, 2008, and December 31, 2020, were recorded and analyzed. RESULTS: Seventy patients with 54 survivors and 16 nonsurvivors were ultimately enrolled. Levels of mHLA-DR in the nonsurvivors (41.8% [38.1-68.1]%) were significantly lower than those in the survivors (83.1% [67.6-89.4]%, p < 0.001). Multivariate logistic regression indicated that mHLA-DR (odds ratio [OR] = 0.939; 95% confidence interval [CI]: 0.892-0.988; p = 0.016) and Glasgow coma scale (GCS) scores (OR = 0.726; 95% CI: 0.591-0.892; p = 0.002) were independent risk factors related with in-hospital mortality rate in EHS. A nomogram incorporated mHLA-DR with GCS demonstrated excellent discrimination and calibration abilities. Compared to the traditional scoring systems, the prediction model incorporated mHLA-DR with GCS had the highest area under the curve (0.947, 95% CI: [0.865-0.986]) and Youden index (0.8333), with sensitivity of 100% and specificity of 83.33%, and a greater clinical net benefit. CONCLUSION: Patients with EHS were at a risk of early experiencing decreased mHLA-DR early. A nomogram based on mHLA-DR with GCS was developed to facilitate early identification and timely treatment of individuals with potentially poor prognosis.