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Background: Several COVID-19 vaccines were developed and approved in China. Of these, the BIBB-CorV and CoronaVac inactivated whole-virion vaccines were widely distributed in China and developing countries. However, the performance of the two vaccines in the real world has not been summarized. Methods: A living systematic review based on findings from ongoing post-licensure studies was conducted, applying standardized algorithms. Articles published between 1 May 2020 and 31 May 2022 in English and Chinese were searched for in Medline, Embase, WanFang Data, medRxiv, bioRxiv, arXiv, SSRN, and Research Square, using SARS-CoV-2, COVID-19, and vaccine as the MeSH terms. Studies with estimates of safety, immunogenicity, and effectiveness from receiving the BIBB-CorV or CoronaVac vaccine that met the predefined screening criteria underwent a full-text review. The Joanna Briggs Institute’s Critical Appraisal Checklist and the Cochrane risk of bias were used for assessment of the quality. A random-effects meta-regression model was applied to identify the potential impact factors on the vaccines’ effectiveness. Results: In total, 32578 articles were identified, of these, 770 studies underwent a full-text review. Eventually, 213 studies were included. The pooled occurrence of solicited and unsolicited adverse events after any dose of either vaccine varied between 10% and 40%. The top five commonly reported rare adverse events were immunization stress-related responses (211 cases, 50.0%), cutaneous responses (43 cases, 10.2%), acute neurological syndrome (39 cases, 9.2%), anaphylaxis (17 cases, 4.0%), and acute stroke (16 cases, 3.8%). The majority (83.3%) recovered or were relieved within several days. The peak neutralization titers against the ancestral strain was found within 1 month after the completion of the primary series of either vaccine, with a GMT (geometric mean titer) of 43.7 (95% CI: 23.2–82.4), followed by a dramatic decrease within 3 months. At Month 12, the GMT was 4.1 (95% CI: 3.8–4.4). Homologous boosting could restore humoral immunity, while heterologous boosting elicited around sixfold higher neutralization titers in comparison with homologous boosting. The effectiveness of receiving either vaccine against death and severe disease was around 85% for both shortly after the primary series. At Month 12, the protection against death did not decline, while the protection against severe disease decreased to ~75%. Conclusions: Both the BIBP-CorV and CoronaVac inactivated vaccines are safe. Sustained vaccine effectiveness against death was determined 12 months after the primary series, although protection against severe disease decreased slightly over time. A booster dose could strengthen the waning effectiveness; however, the duration of the incremental effectiveness and the additional benefit provided by a heterologous booster need to be studied.

Background: Arachnoid cysts (AC) may cause hydrocephalus and neurological symptoms, necessitating surgical intervention. Cyst drainage may result in postoperative complications, however, these interventions are not normally associated with the subsequent development of acute hydrocephalus. Herein, we present two unique cases of AC drainage with postoperative development of acute communicating hydrocephalus. Case Description: Case 1. A 75-year-old female presented with progressive headaches, cognitive decline, and questionable seizures. Her neurological examination was non-focal, but a head computed tomography scan (CT) identified a large right frontal AC with mass effect. She subsequently underwent craniotomy and decompression of the cyst. Postoperatively, her neurological examination deteriorated, and a head CT demonstrated new communicating hydrocephalus. The opening pressure was elevated upon placement of an external ventricular drain. Her hydrocephalus improved on follow-up imaging, but her neurological examination failed to improve, and she ultimately expired. Case 2. A 61-year-old female presented with headache and seizures attributed to a left parietal AC. She underwent open craniotomy for fenestration of the cyst into the Sylvian fissure. Postoperatively, her neurologic examination deteriorated, and she developed acute communicating hydrocephalus. She was initially managed with external ventricular drainage (EVD). The hydrocephalus resolved after several days, and the EVD was subsequently removed. Late follow-up imaging at 2 years showed that the regression of the AC was maintained. Conclusion: Acute development of hydrocephalus is a potential complication of intracranial AC fenestration. A better understanding of intracranial cerebrospinal fluid flow dynamics may better inform as to the underlying cause of this complication. [ABSTRACT FROM AUTHOR]

Abstract Background Gout results from disturbed uric acid metabolism, which causes urate crystal deposition in joints and surrounding tissues. Gout pain management is largely limited to colchicine and nonsteroidal anti-inflammatory drugs. Constant usage of these medications leads to severe side effects. We previously showed electroacupuncture (EA) is effective for relieving pain in animal model of gout arthritis. Here we continued to study the mechanisms underlying how EA alleviates gout pain. Methods Monosodium urate was injected into ankle joint to establish gout arthritis model in mice. EA or sham EA was applied at ST36 and BL60 acupoints of model animals. Biochemical assays, immunostaining, live cell Ca2+ imaging and behavioral assays were applied. Results Model mice displayed obvious mechanical allodynia, accompanied with gait impairments. EA attenuated mechanical hypersensitivities and improved gait impairments. EA reduced the overexpression of NLRP3 inflammasome signaling molecules in ankle joints of model animals. EA-induced anti-allodynia, as well as inhibition on NLRP3 inflammasome, were mimicked by antagonizing but abolished by activating NLRP3 inflammasome via pharmacological methods. EA attenuated oxidative stress, an upstream signaling of NLRP3 inflammasome in ankle joints of model mice. Exogenously increasing oxidative stress abolished EA’s inhibitory effect on NLRP3 inflammasome and further reversed EA’s anti-allodynic effect. EA reduced neutrophil infiltrations in ankle joint synovium, a major mechanism contributing to oxidative stress in gout. Pharmacological blocking NLRP3 inflammasome or EA reduced TRPV1 channel overexpression in dorsal root ganglion (DRG) neurons. Ca2+ imaging confirmed that EA could reduce functional enhancement in TRPV1 channel in DRG neurons during gout. Conclusions Our results demonstrate that EA reduces gout pain possibly through suppressing ROS-mediated NLRP3 inflammasome activation in inflamed ankle joints and TRPV1 upregulation in sensory neurons, supporting EA as a treatment option for gout pain.

Warming and increased CO2 levels are generally believed to enhance photosynthetic rates (A) and tree growth, especially in alpine treelines. However, this positive effect may be limited by moisture availability. Here we compare the radial growth and intrinsic water use efficiency (iWUE) of two widely-distributed evergreen needleleaf species, Tibetan juniper (Juniperus tibetica) and Balfour spruce (Picea balfouriana), at the same site near the treeline on the southeastern Tibetan Plateau using tree-ring width and dual isotopes (δ13C and δ18O). We observed that with a 70-ppm increase in atmospheric CO2 from 1954 to 2007, juniper radial growth was significantly stimulated, whereas spruce growth remained constant. Correlation analysis between tree-ring width and climate factors revealed that spruce was more moisture-sensitive than juniper. Although the increases in iWUE for juniper (22%) and spruce (26%) were similar, iWUE changes in spruce were more influenced by stomatal conductance (gs) rather than A, supporting that moisture availability inhibits spruce growth. Our study implies that predicting growth dynamics in alpine forests based on the growth-temperature relationship may be inadequate, as they are likely moisture-limited. It also suggests that increases in A may not be as widespread as previously thought, which helps improve forest productivity modeling.

The intestinal and intratumoral microbiota are closely associated with tumor progression and response to antitumor treatments. The antibacterial or tumor microenvironment (TME)-modulating approaches have been shown to markedly improve antitumor efficacy, strategies focused on normalizing the microbial environment are rarely reported. Here, we reported the development of an orally administered inulin-based hydrogel with colon-targeting and retention effects, containing hollow MnO2 nanocarrier loaded with the chemotherapeutic drug Oxa (Oxa@HMI). On the one hand, beneficial bacteria in the colon specifically metabolized Oxa@HMI, resulting in the degradation of inulin and the generation of short-chain fatty acids (SCFAs). These SCFAs play a crucial role in modulating microbiota and stimulating immune responses. On the other hand, the hydrogel matrix underwent colon microbiota-specific degradation, enabling the targeted release of Oxa and production of reactive oxygen species in the acidic TME. In this study, we have established, for the first time, a microbiota-targeted drug delivery system Oxa@HMI that exhibited high efficiency in colorectal cancer targeting and colon retention. Oxa@HMI promoted chemotherapy efficiency and activated antitumor immune responses by intervening in the microbial environment within the tumor tissue, providing a crucial clinical approach for the treatment of colorectal cancer that susceptible to microbial invasion.

Abstract Background Complex regional pain syndrome type-I (CRPS-I) causes excruciating pain that affect patients’ life quality. However, the mechanisms underlying CRPS-I are incompletely understood, which hampers the development of target specific therapeutics. Methods The mouse chronic post-ischemic pain (CPIP) model was established to mimic CRPS-I. qPCR, Western blot, immunostaining, behavioral assay and pharmacological methods were used to study mechanisms underlying neuroinflammation and chronic pain in spinal cord dorsal horn (SCDH) of CPIP mice. Results CPIP mice developed robust and long-lasting mechanical allodynia in bilateral hindpaws. The expression of inflammatory chemokine CXCL13 and its receptor CXCR5 was significantly upregulated in ipsilateral SCDH of CPIP mice. Immunostaining revealed CXCL13 and CXCR5 was predominantly expressed in spinal neurons. Neutralization of spinal CXCL13 or genetic deletion of Cxcr5 (Cxcr5 −/−) significantly reduced mechanical allodynia, as well as spinal glial cell overactivation and c-Fos activation in SCDH of CPIP mice. Mechanical pain causes affective disorder in CPIP mice, which was attenuated in Cxcr5 −/− mice. Phosphorylated STAT3 co-expressed with CXCL13 in SCDH neurons and contributed to CXCL13 upregulation and mechanical allodynia in CPIP mice. CXCR5 coupled with NF-κB signaling in SCDH neurons to trigger pro-inflammatory cytokine gene Il6 upregulation, contributing to mechanical allodynia. Intrathecal CXCL13 injection produced mechanical allodynia via CXCR5-dependent NF-κB activation. Specific overexpression of CXCL13 in SCDH neurons is sufficient to induce persistent mechanical allodynia in naïve mice. Conclusions These results demonstrated a previously unidentified role of CXCL13/CXCR5 signaling in mediating spinal neuroinflammation and mechanical pain in an animal model of CRPS-I. Our work suggests that targeting CXCL13/CXCR5 pathway may lead to novel therapeutic approaches for CRPS-I.

PURPOSE: Aneurysmal recurrence represents a significant drawback of endovascular coiling, particularly in aneurysms that have previously ruptured. Given the high recurrence rate of coiled aneurysms and particularly the risk of posttreatment rupture in previously ruptured aneurysms that have been treated by coiling, the question of how best to treat ruptured aneurysms that recur postcoiling remains. MATERIALS AND METHODS: We conducted a retrospective analysis of twenty patients who underwent pipeline embolization of previously ruptured, coiled cerebral aneurysms. RESULTS: Pipeline embolization device (PED) treatment resulted in complete aneurysmal occlusion in 10 patients (62.5%) at first angiographic follow-up, and 11 patients (68.75%) at last follow-up. No PED-related complications were encountered and there were no peri-procedural or postprocedural hemorrhages, or symptomatic ischemic events following flow diversion. CONCLUSIONS: PED as a second-line treatment is a safe and effective modality for achieving aneurysmal occlusion in recurrent, previously ruptured, primarily coiled aneurysms. Additionally, a staged coil-to-PED approach may be considered for the management of acutely ruptured aneurysms to achieve aneurysmal obliteration in an effort to mitigate recurrence, and reduce the amount of postprocedural studies. [ABSTRACT FROM AUTHOR]

Industrialization has increased global carbon emissions, necessitating effective climate change mitigation measures. China, the most populous developing nation, faces the challenge of strategizing emissions to meet national carbon neutrality objectives. However, research on specific regions’ carbon emissions drivers and causal factors is limited, particularly across prefectural-level cities. This study estimates the spatial and temporal patterns of carbon emissions across China’s prefectural cities and utilizes both OLS regression and stepwise regression models to analyze the impact of various factors influencing carbon emissions in these cities. Results reveal the following: (1) The country’s overall 20-year carbon emissions continue to grow from 3020.29 Mt in 2001 to 9169.74 Mt in 2020, with an average annual growth rate of 5.71%; the eastern region has seen a gradual deceleration in emissions, whereas the western region continues to experience an increase. Carbon emissions in cities within each subregion consistently rise. (2) Carbon emissions in Chinese prefectural-level cities exhibit strong spatial autocorrelation and clustering (Z > 1.96, p < 0.05), with hot spots primarily in the eastern coastal areas and cold spots in the northwest to southwest regions. (3) Economic and demographic factors significantly increase carbon emissions, while climate and urbanization effects are more complex and variable. Economic growth and population increase are the most significant influencing factors, but regional variances exist in carbon emissions determinants in subregional prefectural cities. These insights provide valuable insights into national emission dynamics at the prefectural level, providing a theoretical basis for enhancing carbon emission strategies across various jurisdictions.

PurposeOur aim was to conduct a meta-analysis and systematic review in order to compare the diagnostic efficacy of 68Ga-PSMA-11 PET/CT and 68Ga-PSMA-11 PET/MRI in patients with biochemically recurrent after radical prostatectomy and biochemically recurrent prostate cancers (BCR) after hybrid RT and RP.MethodsUp until February 2023, we searched PubMed, Embase, and Web of Science for pertinent papers. Studies examining the utility of 68Ga-PSMA-11 PET/CT or PET/MRI as a screening tool for biochemically recurrent prostate cancer were included. To measure heterogeneity, we employed the I2 statistic. In cases of substantial heterogeneity (I2 > 50%), we used the random effect model to produce a forest plot. In other cases, we utilized the fixed model. Furthermore, we assessed the quality of the studies included using the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) method.ResultsIn total, 37 studies involving 8409 patients were examined. For 68Ga-PSMA-11 PET/CT and 68Ga-PSMA-11 PET/MRI, the combined total detection rate was 0.70 (95% CI: 0.65-0.75) and 0.71 (95% CI:0.67-0.75), respectively. 68Ga-PSMA-11 PET/CT and 68Ga-PSMA-11 PET/MRI did not substantially differ in terms of the overall detection rate for BCR (P = 0.58). The detection rate was unaffected by the PSA values (all P > 0.05).ConclusionThe diagnostic efficacy of 68Ga-PSMA-11 PET/CT appears to be equivalent to that of 68Ga-PSMA-11 PET/MRI in detecting biochemically recurrent prostate cancer. Nonetheless, it should be noted that not all studies have used pathological biopsies as the gold standard. Therefore, additional larger prospective studies are needed to address this issue.Systematic review registrationidentifier CRD42023410039.

Abstract Soil conservation is of global importance, as accelerated soil erosion by human activity is a primary threat to ecosystem viability. However, the significance and role of soil conservation in reshaping landscape carbon (C) accounting has not been comprehensively integrated in the terrestrial C sink. Here, we present the first integrated assessment of the modified terrestrial C sink and aquatic C transport due to soil conservation for the semiarid Chinese Loess Plateau (CLP), the world's most vulnerable region to soil erosion. We show a surprisingly low terrestrial‐aquatic C transfer that offset the terrestrial net ecosystem productivity by only 7.5%, which we attribute to the effective implementation of soil conservation practices. Despite the highest soil erosion, the semiarid CLP acts as effective C sink at 43.2 ± 22.6 g C m−2 year−1, which is comparable to temperate forest in absorbing atmospheric CO2. Moreover, C burial in reservoirs has created an additional anthropogenic C sink of 2.9 ± 1.1 g C m−2 year−1. Our findings indicate that effective soil conservation can significantly increase landscape C sequestration capacity. The co‐benefits of soil conservation in erosion control and C sequestration have important implications for policy makers in other regions undergoing increasing erosion intensity to pursue environmental sustainability.

Summary: The dorsal bed nucleus of stria terminalis (dBNST) is a pivotal hub for stress response modulation. Dysfunction of dopamine (DA) network is associated with chronic stress, but the roles of DA network of dBNST in chronic stress-induced emotional disorders remain unclear. We examine the role of dBNST Drd1+ and Drd2+ neurons in post-weaning social isolation (PWSI)-induced behavior deficits. We find that male, but not female, PWSI rats exhibit negative emotional phenotypes and the increase of excitability and E-I balance of dBNST Drd2+ neurons. More importantly, hypofunction of dBNST Drd2 receptor underlies PWSI-stress-induced male-specific neuronal plasticity change of dBNST Drd2+ neurons. Furthermore, chemogenetic activation of dBNST Drd2+ neurons is sufficient to induce anxiogenic effects, while Kir4.1-mediated chronic inhibition of dBNST Drd2+ neurons ameliorate PWSI-induced anxiety-like behaviors. Our findings reveal an important neural mechanism underlying PWSI-induced sex-specific behavioral abnormalities and potentially provide a target for the treatment of social stress-related emotional disorder.

Summary: The impacts of low soil moisture (SM) and high vapour pressure deficit (VPD) on tree’s photosynthesis and productivity are ultimately realized by changing water content in the canopy leaves. In this study, variations in canopy water content (CWC) that can be detected from microwave remotely sensed vegetation optical depth (VOD) have been proposed as a promising measure of vegetation water status, and we first reported that the regulation of CWC on productivity stability is universally applicable for global forests. Results of structural equation model (SEM) also confirmed the significant negative effect of CWC on coefficient of variation (CV) of productivity, indicating that the decrease in CWC could inevitably induce the instability of forest productivity under climate change. The most significant decrease (p

Over the last several decades, China has taken multiple measures for afforestation and natural forest protection, including setting the goal of carbon neutrality by the middle of 21th century. In order to support the practice of relevant policies from the scientific perspective, it is essential to precisely estimate the carbon storage of arbor forest, as it plays an important role in the carbon cycle of ecosystems. In this study, we first used the latest four phases of national forest inventory data to investigate the variation of carbon storage for both natural and planted arbor forest in China during the covered period (1999-2018). Then we used machine leaning methods to simulate the carbon density based on various kinds of environmental factors and analyzed the contribution of each influencing factor. Our results demonstrate that the total carbon storage for arbor forest in China kept increasing over the last two decades, but this increment was mainly brought about by the continuous expansion of forest land. The gap of carbon sequestration between natural forest and planted forest showed a significant trend of reduction. Additionally, tree age was identified as the dominant factor for influencing the spatiotemporal variation of carbon density among all the independent variables while the impact of climatic factor was limited. Therefore, the future improvement of carbon sequestration of arbor forest in should mainly rely on additional projects of afforestation, reforestation, green space conservation and reduction of emissions in China. Conclusions of this study have important implications for policy makers and other stakeholders to evaluate the previous achievement of environmental projects and can also help to set future plans and finally realize the goals of carbon neutrality.

IntroductionLateral ankle sprain (LAS) is a very common type of joint injury. It occurred with high incidence among general population and especially among individuals participating sports and outdoor activities. A certain proportion of individuals who once developed LAS may suffer persistent ankle pain that affects daily activities. However, the mechanisms underlying LAS-induced pain still remained largely unknown.MethodsWe established a LAS mouse model and systematically evaluated the pain-related behaviors in this mouse model. RNA sequencing (RNA-Seq), combined with bioinformatics analysis, was undertaken to explore gene expression profiles. Immunostaining was used to study glial cell and neuron activation in ipsilateral spinal cord dorsal horn (SCDH) of LAS model mice. Ibuprofen was used to treat LAS model mice.ResultsThe LAS model mice developed obvious signs of mechanical and heat hypersensitivities as well as gait impairments in ipsilateral hind paws. Besides, LAS model mice developed signs of pain-related emotional disorder, including pain-induced aversion. By RNA-Seq, we were able to identify certain differentially expressed genes and signaling pathways that might contribute to pain mechanisms of LAS mouse model. In addition, LAS model mice showed increased c-Fos and p-ERK immunoreactivity as well as astrocyte and microglia overactivation in ipsilateral spinal cord dorsal horn, indicating central sensitization might occur. Finally, LAS model mice respond to ibuprofen, a drug clinically used to treat ankle sprain pain.ConclusionOur study found LAS model mice may be used as a preclinical animal model for screening novel targets or therapies for ankle sprain. Thus, the study may further help to understand molecular mechanisms contributing to ankle sprain-induced pain.

China is one of the countries with the largest citrus cultivation areas, and its citrus industry has received significant attention due to its substantial economic benefits. Traditional manual forestry surveys and remote sensing image classification tasks are labor-intensive and time-consuming, resulting in low efficiency. Remote sensing technology holds great potential for obtaining spatial information on citrus orchards on a large scale. This study proposes a lightweight model for citrus plantation extraction that combines the DeepLabV3+ model with the convolutional block attention module (CBAM) attention mechanism, with a focus on the phenological growth characteristics of citrus in the Guangxi region. The objective is to address issues such as inaccurate extraction of citrus edges in high-resolution images, misclassification and omissions caused by intra-class differences, as well as the large number of network parameters and long training time found in classical semantic segmentation models. To reduce parameter count and improve training speed, the MobileNetV2 lightweight network is used as a replacement for the Xception backbone network in DeepLabV3+. Additionally, the CBAM is introduced to extract citrus features more accurately and efficiently. Moreover, in consideration of the growth characteristics of citrus, this study augments the feature input with additional channels to better capture and utilize key phenological features of citrus, thereby enhancing the accuracy of citrus recognition. The results demonstrate that the improved DeepLabV3+ model exhibits high reliability in citrus recognition and extraction, achieving an overall accuracy (OA) of 96.23%, a mean pixel accuracy (mPA) of 83.79%, and a mean intersection over union (mIoU) of 85.40%. These metrics represent an improvement of 11.16%, 14.88%, and 14.98%, respectively, compared to the original DeepLabV3+ model. Furthermore, when compared to classical semantic segmentation models, such as UNet and PSPNet, the proposed model achieves higher recognition accuracy. Additionally, the improved DeepLabV3+ model demonstrates a significant reduction in both parameters and training time. Generalization experiments conducted in Nanning, Guangxi Province, further validate the model’s strong generalization capabilities. Overall, this study emphasizes extraction accuracy, reduction in parameter count, adherence to timeliness requirements, and facilitation of rapid and accurate extraction of citrus plantation areas, presenting promising application prospects.

Abstract Background Allergic contact dermatitis (ACD) is a common skin condition characterized by contact hypersensitivity to allergens, accompanied with skin inflammation and a mixed itch and pain sensation. The itch and pain dramatically affects patients’ quality of life. However, still little is known about the mechanisms triggering pain and itch sensations in ACD. Methods We established a mouse model of ACD by sensitization and repetitive challenge with the hapten oxazolone. Skin pathological analysis, transcriptome RNA sequencing (RNA-seq), qPCR, Ca2+ imaging, immunostaining, and behavioral assay were used for identifying gene expression changes in dorsal root ganglion innervating the inflamed skin of ACD model mice and for further functional validations. Results The model mice developed typical ACD symptoms, including skin dryness, erythema, excoriation, edema, epidermal hyperplasia, inflammatory cell infiltration, and scratching behavior, accompanied with development of eczematous lesions. Transcriptome RNA-seq revealed a number of differentially expressed genes (DEGs), including 1436-DEG mRNAs and 374-DEG-long noncoding RNAs (lncRNAs). We identified a number of DEGs specifically related to sensory neuron signal transduction, pain, itch, and neuroinflammation. Comparison of our dataset with another published dataset of atopic dermatitis mouse model identified a core set of genes in peripheral sensory neurons that are exclusively affected by local skin inflammation. We further found that the expression of the pain and itch receptor MrgprD was functionally upregulated in dorsal root ganglia (DRG) neurons innervating the inflamed skin of ACD model mice. MrgprD activation induced by its agonist β-alanine resulted in exaggerated scratching responses in ACD model mice compared with naïve mice. Conclusions We identified the molecular changes and cellular pathways in peripheral sensory ganglia during ACD that might participate in neurogenic inflammation, pain, and itch. We further revealed that the pain and itch receptor MrgprD is functionally upregulated in DRG neurons, which might contribute to peripheral pain and itch sensitization during ACD. Thus, targeting MrgprD may be an effective method for alleviating itch and pain in ACD.

Chronic pain is one of the most common clinical syndromes affecting patients’ quality of life. Regulating the transition from acute to chronic pain is a novel therapeutic strategy for chronic pain that presents a major clinical challenge. However, the mechanism underlying pain transitions remains poorly understood. A rat hyperalgesic priming (HP) model, which mimics pain transition, was established decades ago. Here, this HP model and RNA sequencing (RNA-seq) were used to study the potential role of neuroinflammation in pain transition. In this study, HP model rats developed prolonged hyperalgesia in the hind paw after carrageenan (Car) and PGE2 injection, accompanied by obvious satellite glial cell (SGC) activation in the dorsal root ganglion (DRG), as indicated by upregulation of GFAP. RNA-Seq identified a total of differentially expressed genes in the ipsilateral DRG in HP model rats. The expression of several representative genes was confirmed by real-time quantitative PCR (qPCR). Functional analysis of the differentially expressed genes indicated that genes related to the inflammatory and neuroinflammatory response showed the most significant changes in expression. We further found that the expression of the chemokine CXCL1 was significantly upregulated in the rat DRG. Pharmacological blockade of CXCL1 reduced protein kinase C epsilon overproduction as well as hyperalgesia in HP rats but did not prevent the upregulation of GFAP in the DRG. These results reveal that neuroinflammatory responses are involved in pain transition and may be the source of chronic pain. The chemokine CXCL1 in the DRG is a pivotal contributor to chronic pain and pain transition in HP model rats. Thus, our study provides a putative novel target for the development of effective therapeutics to prevent pain transition.

The Tibetan Plateau (TP), known as the third pole, is the highest plateau in the world. It has numerous wetlands, which are important ecological security barriers and plays an important role in mitigating global climate change. This paper employed breaks for additive seasonal and trend (BFAST) algorithm for the mutation detection of the monthly normalized difference vegetation index (NDVI) in wetlands. In addition, correlation analysis and residual analysis were used to study the response of climate change and human activities to NDVI of alpine wetland vegetation in the TP during 2000–2015. The results indicate that the NDVI showed a weak upward trend of 0.009/10a (P < 0.05) with the climate presenting a trend of dry heat development. The NDVI of the growing season was greatly affected by temperature factors with the highest correlation coefficient of 0.686 (P < 0.01). The temperature in the month before and solar radiation in the 3 months before also presented a time lag effect on NDVI, and their correlation coefficients were 0.574 (P < 0.05) and 0.636 (P < 0.05), respectively. Additionally, human activities may have a positive impact on the wetland after 2008. This study explored, for the first time, the NDVI variations of the dynamic wetland and their correlations with temperature, precipitation and solar radiation.

Introduction: Fibroblast growth factor homologous factors (FHFs), among other fibroblast growth factors, are increasingly found to be important regulators of ion channel functions. Although FHFs have been link to several neuronal diseases and arrhythmia, its role in inflammatory pain still remains unclear. Objectives: This study aimed to investigate the role and mechanism of FGF13 in inflammatory pain. Methods: Fgf13 conditional knockout mice were generated and CFA-induced chronic inflammatory pain model was established to measure the pain threshold. Immunostaining, western blot and quantitative real-time reverse transcription PCR (qRT-PCR) were performed to detect the expression of FGF13 in CFA-induced inflammatory pain. Whole-cell patch clamp recording was used to record the action potential firing properties and sodium currents of DRG neurons. Results: Conditional knockout of Fgf13 in dorsal root ganglion (DRG) neurons (Fgf13-/Y) led to attenuated pain responses induced by complete Freund's adjuvant (CFA). FGF13 was expressed predominantly in small-diameter DRG neurons. CFA treatment resulted in an increased expression of FGF13 proteins as well as an increased excitability in nociceptive DRG neurons which was inhibited when FGF13 was absent. The role of FGF13 in neuronal excitability of DRG was linked to its modulation of voltage-gated Na+ channels mediated by microtubules. Overexpression of FGF13, but not FGF13 mutant which lacks the ability to bind and stabilize microtubules, rescued the decreased neuronal excitability and Na+ current density in DRG neurons of Fgf13-/Y mice. Conclusion: This study revealed that FGF13 could stabilize microtubules to modulate sodium channel function in DRG neurons and modulate inflammatory pain. This study provides a novel mechanism for FGF13 modulation of sodium channel function and suggests that FGF13 might be a novel target for inflammatory pain treatment.

Abstract Climate sensitivity of vegetation has long been explored using statistical or process‐based models. However, great uncertainties still remain due to the methodologies’ deficiency in capturing the complex interactions between climate and vegetation. Here, we developed global gridded climate–vegetation models based on long short‐term memory (LSTM) network, which is a powerful deep‐learning algorithm for long‐time series modeling, to achieve accurate vegetation monitoring and investigate the complex relationship between climate and vegetation. We selected the normalized difference vegetation index (NDVI) that represents vegetation greenness as model outputs. The climate data (monthly temperature and precipitation) were used as inputs. We trained the networks with data from 1982 to 2003, and the data from 2004 to 2015 were used to validate the models. Error analysis and sensitivity analysis were performed to assess the model errors and investigate the sensitivity of global vegetation to climate change. Results show that models based on deep learning are very effective in simulating and predicting the vegetation greenness dynamics. For models training, the root mean square error (RMSE) is

As more machine learning and deep learning models are applied in studying the quantitative relationship between the climate and terrestrial vegetation growth, the uncertainty of these advanced models requires clarification. Partial dependence plots (PDPs) are one of the most widely used methods to estimate the marginal effect of independent variables on the predicted outcome of a machine learning model, and it is regarded as the main basis for conclusions in relevant research. As more controversies regarding the reliability of the results of the PDPs emerge, the uncertainty of the PDPs remains unclear. In this paper, we experiment with real, remote sensing data to systematically analyze the uncertainty of partial dependence relationships between four climate variables (temperature, rainfall, radiation, and windspeed) and vegetation growth, with one conventional linear model and six machine learning models. We tested the uncertainty of the PDP curves across different machine learning models from three aspects: variation, whole linear trends, and the trait of change points. Results show that the PDP of the dominant climate factor (mean air temperature) and vegetation growth parameter (indicated by the normalized difference vegetation index, NDVI) has the smallest relative variation and the whole linear trend of the PDP was comparatively stable across the different models. The mean relative variation of change points across the partial dependence curves of the non-dominant climate factors (i.e., radiation, windspeed, and rainfall) and vegetation growth ranged from 8.96% to 23.8%, respectively, which was much higher than those of the dominant climate factor and vegetation growth. Lastly, the model used for creating the PDP, rather than the relative importance of these climate factors, determines the fluctuation of the PDP output of these climate variables and vegetation growth. These findings have significant implications for using remote sensing data and machine learning models to investigate the quantitative relationships between the climate and terrestrial vegetation.

Abstract Chronic pain affects the life quality of the suffering patients and posts heavy problems to the health care system. Conventional medications are usually insufficient for chronic pain management and oftentimes results in many adverse effects. The NLRP3 inflammasome controls the processing of proinflammatory cytokine interleukin 1β (IL-1β) and is implicated in a variety of disease conditions. Recently, growing number of evidence suggests that NLRP3 inflammasome is dysregulated under chronic pain condition and contributes to pathogenesis of chronic pain. This review provides an up-to-date summary of the recent findings of the involvement of NLRP3 inflammasome in chronic pain and discussed the expression and regulation of NLRP3 inflammasome-related signaling components in chronic pain conditions. This review also summarized the successful therapeutic approaches that target against NLRP3 inflammasome for chronic pain treatment.

Abstract Background Paclitaxel is a widely prescribed chemotherapy drug for treating solid tumors. However, paclitaxel-induced peripheral neuropathy (PIPN) is a common adverse effect during paclitaxel treatment, which results in sensory abnormalities and neuropathic pain among patients. Unfortunately, the mechanisms underlying PIPN still remain poorly understood. Long noncoding RNAs (lncRNAs) are novel and promising targets for chronic pain treatment, but their involvement in PIPN still remains unexplored. Methods We established a rat PIPN model by repetitive paclitaxel application. Immunostaining, RNA sequencing (RNA-Seq) and bioinformatics analysis were performed to study glia cell activation and explore lncRNA/mRNA expression profiles in spinal cord dorsal horn (SCDH) of PIPN model rats. qPCR and protein assay were used for further validation. Results PIPN model rats developed long-lasting mechanical and thermal pain hypersensitivities in hind paws, accompanied with astrocyte and microglia activation in SCDH. RNA-Seq identified a total of 814 differentially expressed mRNAs (DEmRNA) (including 467 upregulated and 347 downregulated) and 412 DElncRNAs (including 145 upregulated and 267 downregulated) in SCDH of PIPN model rats vs. control rats. Functional analysis of DEmRNAs and DElncRNAs identified that the most significantly enriched pathways include immune/inflammatory responses and neurotrophin signaling pathways, which are all important mechanisms mediating neuroinflammation, central sensitization, and chronic pain. We further compared our dataset with other published datasets of neuropathic pain and identified a core set of immune response-related genes extensively involved in PIPN and other neuropathic pain conditions. Lastly, a competing RNA network analysis of DElncRNAs and DEmRNAs was performed to identify potential regulatory networks of lncRNAs on mRNA through miRNA sponging. Conclusions Our study provided the transcriptome profiling of DElncRNAs and DEmRNAs and uncovered immune and inflammatory responses were predominant biological events in SCDH of the rat PIPN model. Thus, our study may help to identify promising genes or signaling pathways for PIPN therapeutics.

Complex regional pain syndrome type-I (CRPS-I) is a chronic neurological disorder that results in severe pain and affects patients' life quality. Conventional therapies usually lack effectiveness. Electroacupuncture (EA) is an effective physical therapy for relieving CRPS-I pain. However, the mechanism underlying EA-induced analgesia on CRPS-I still remain unknown. Spinal NLRP3 inflammasome was recently identified to contribute to pain and neuroinflammation in a rat model of CRPS-I by our group. Here, we aimed to study whether EA could inhibit spinal NLRP3 inflammasome activation, thus resulting in pain relief and attenuation of spinal neuroinflammation in the rat model of CRPS-I. We established the rat chronic post-ischemic pain (CPIP) model to mimic CRPS-I. CPIP rats developed remarkable mechanical allodynia that could be relieved by daily EA intervention. NLRP3 inflammasome was activated in spinal cord dorsal horn (SCDH) of CPIP rats, accompanied with over-production of pro-inflammatory cytokine IL-1β. Immunostaining revealed that the cellular distribution of NLRP3 was predominantly located in SCDH neurons. Pharmacological activation of NLRP3 inflammasome per se is sufficient to produce persistent mechanical allodynia in naïve animals, whereas blocking NLRP3 inflammasome attenuates mechanical allodynia of CPIP rats. EA exclusively reduced NLRP3 overexpression in SCDH neurons and attenuated spinal glial cell over-activation in CPIP rats. EA-induced anti-allodynia with attenuation of spinal glial cell over-activation were all mimicked by intrathecal blocking NLRP3 inflammasome and reversed by activating NLRP3 inflammasome, respectively, through pharmacological methods. Finally, spinal blocking IL-1β attenuated mechanical allodynia and spinal glial cell over-activation in CPIP rats, resembling the effects of EA. In all, these results demonstrate that spinal NLRP3 inflammasome activation contributes to mechanical allodynia of the rat model of CRPS-I and EA ameliorates mechanical allodynia through inhibiting NLRP3 inflammasome activation in SCDH neurons. Our study further supports EA can be used as an effective treatment for CRPS-I.

Abstract Background Complex regional pain syndrome type-I (CRPS-I) is a progressive and devastating pain condition. The mechanisms of CRPS-I still remain poorly understood. We aim to explore expression profiles of genes relevant to pain and neuroinflammation mechanisms involved in CRPS-I. Methods The rat chronic post-ischemic pain (CPIP) model that mimics human CRPS-I was established. RNA-sequencing (RNA-Seq), qPCR, Western blot, immunostaining, and pharmacological studies were used for profiling gene changes in ipsilateral spinal cord dorsal horn (SCDH) of CPIP model rat and further validation. Results CPIP rats developed persistent mechanical allodynia in bilateral hind paws, accompanied with obvious glial activation in SCDH. RNA-Seq identified a total of 435 differentially expressed genes (DEGs) in ipsilateral SCDH of CPIP rats. qPCR confirmed the expression of several representative genes. Functional analysis of DEGs identified that the most significantly enriched biological processes of upregulated genes include inflammatory and innate immune response. We further identified NLRP3 inflammasome expression to be significantly upregulated in SCDH of CPIP rats. Pharmacological blocking NLRP3 inflammasome reduced IL-1β overproduction, glial activation in SCDH as well as mechanical allodynia of CPIP rats. Conclusion Our study revealed that immune and inflammatory responses are predominant biological events in SCDH of CPIP rats. We further identified NLRP3 inflammasome in SCDH as a key contributor to the pain and inflammation responses in CPIP rats. Thus, our study provided putative novel targets that may help to develop effective therapeutics against CRPS-I.

High-gradient headwater streams are major participants in the carbon (C) cycle because of their capabilities of emitting a significant amount of carbon dioxide (CO2). Notwithstanding, their CO2 emissions have been largely overlooked in previous studies owing to their small water surface area and are sometimes strenuous to be measured because of their narrow channel widths and strong turbulence. This study examined the spatial and seasonal variabilities of CO2 dynamics of a subtropical steep headwater stream fed by groundwater. Our study found that the pH and dissolved oxygen exhibited a general increasing trend away from the source of the headwater whereas the partial pressure of carbon dioxide (pCO2) showed a downward trend. The stream water pCO2 in the upper reach was found to be higher than the ambient level by 19–114 times, with an average drop of >70% at just 9.2 m from the groundwater source, demonstrating the potentially large emission of CO2 into the atmosphere within this short distance. Additionally, the sampling works conducted further downstream revealed that the CO2 derived from groundwater could almost completely dissipate within approximately half a kilometer downstream of the source. The concentrations of dissolved organic carbon and pCO2 were also lower during the period with lower air temperatures in the headwater stream, indicating temperature-dependent metabolism and decomposition of organic matter in soil might modulate the C dynamics in the headwater stream, although the rapid gas exchange along the stream remained the determinative factor. Our findings reassert that headwater streams are an essential source of CO2 and disregarding them from the studies of greenhouse gas emissions of inland waters would underestimate their potency to influence the global C cycle.

Background: Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs), but risk factors for COVID-19-associated IPA (CAPA) have not been fully characterized. The aim of the current study was to identify factors associated with CAPA, and assess long-term mortality.Methods: A retrospective cohort study of adult COVID-19 patients admitted to ICUs from six hospitals was conducted in Hubei, China. CAPA was diagnosed via composite clinical criteria. Demographic information, clinical variables, and 180-day outcomes after the diagnosis of CAPA were analyzed.Results: Of 335 critically ill patients with COVID-19, 78 (23.3%) developed CAPA within a median of 20.5 days (range 13.0–42.0 days) after symptom onset. Compared to those without CAPA, CAPA patients were more likely to have thrombocytopenia (50 vs. 19.5%, p < 0.001) and secondary bacterial infection prior to being diagnosed with CAPA (15.4 vs. 6.2%, p = 0.013), and to receive vasopressors (37.2 vs. 8.6%, p < 0.001), higher steroid dosages (53.9 vs. 34.2%, p = 0.002), renal replacement therapy (37.2 vs. 13.6%, p < 0.001), and invasive mechanical ventilation (57.7 vs. 35.8%, p < 0.001). In multivariate analysis incorporating hazard ratios (HRs) and confidence intervals (CIs), thrombocytopenia (HR 1.98, 95% CI 1.16–3.37, p = 0.012), vasopressor use (HR 3.57, 95% CI 1.80–7.06, p < 0.001), and methylprednisolone use at a daily dose ≥ 40 mg (HR 1.69, 95% CI 1.02–2.79, p = 1.02–2.79) before CAPA diagnosis were independently associated with CAPA. Patients with CAPA had longer median ICU stays (17 days vs. 12 days, p = 0.007), and higher 180-day mortality (65.4 vs. 33.5%, p < 0.001) than those without CAPA.Conclusions: Thrombocytopenia, vasopressor use, and corticosteroid treatment were significantly associated with increased risk of incident IPA in COVID-19 patients admitted to ICUs. The occurrence of CAPA may increase the likelihood of long-term COVID-19 mortality.

Summary: Cooperation is common in nature and is pivotal to the development of human society. However, the details of how and why cooperation evolved remain poorly understood. Cross-species investigation of cooperation may help to elucidate the evolution of cooperative strategies. Thus, we design an automated cooperative behavioral paradigm and quantitatively examine the cooperative abilities and strategies of mice, rats, and tree shrews. We find that social communication plays a key role in the establishment of cooperation and that increased cooperative ability and a more efficient cooperative strategy emerge as a function of the evolutionary hierarchy of the tested species. Moreover, we demonstrate that single-unit activities in the orbitofrontal and prelimbic cortex in rats represent neural signals that may be used to distinguish between the cooperative and non-cooperative tasks, and such signals are distinct from the reward signals. Both signals may represent distinct components of the internal drive for cooperation.