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Abstract Background Interleukin 24 (IL-24) has been implicated in the nociceptive signaling. However, direct evidence and the precise molecular mechanism underlying IL-24’s role in peripheral nociception remain unclear. Methods Using patch clamp recording, molecular biological analysis, immunofluorescence labeling, siRNA-mediated knockdown approach and behavior tests, we elucidated the effects of IL-24 on sensory neuronal excitability and peripheral pain sensitivity mediated by T-type Ca2+ channels (T-type channels). Results IL-24 enhances T-type channel currents (T-currents) in trigeminal ganglion (TG) neurons in a reversible and dose-dependent manner, primarily by activating the interleukin-22 receptor 1 (IL-22R1). Furthermore, we found that the IL-24-induced T-type channel response is mediated through tyrosine-protein kinase Lyn, but not its common downstream target JAK1. IL-24 application significantly activated protein kinase A; this effect was independent of cAMP and prevented by Lyn antagonism. Inhibition of PKA prevented the IL-24-induced T-current response, whereas inhibition of protein kinase C or MAPK kinases had no effect. Functionally, IL-24 increased TG neuronal excitability and enhanced pain sensitivity to mechanical stimuli in mice, both of which were suppressed by blocking T-type channels. In a trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve, inhibiting IL-22R1 signaling alleviated mechanical allodynia, which was reversed by blocking T-type channels or knocking down Cav3.2. Conclusion Our findings reveal that IL-24 enhances T-currents by stimulating IL-22R1 coupled to Lyn-dependent PKA signaling, leading to TG neuronal hyperexcitability and pain hypersensitivity. Understanding the mechanism of IL-24/IL-22R1 signaling in sensory neurons may pave the way for innovative therapeutic strategies in pain management.

Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response.

Abstract Although beta-endorphinergic neurons in the hypothalamic arcuate nucleus (ARC) synthesize beta-endorphin (β-EP) to alleviate nociceptive behaviors, the underlying regulatory mechanisms remain unknown. Here, we elucidated an epigenetic pathway driven by microRNA regulation of β-EP synthesis in ARC neurons to control neuropathic pain. In pain-injured rats miR-203a-3p was the most highly upregulated miRNA in the ARC. A similar increase was identified in the cerebrospinal fluid of trigeminal neuralgia patients. Mechanistically, we found histone deacetylase 9 was downregulated following nerve injury, which decreased deacetylation of histone H3 lysine-18, facilitating the binding of NR4A2 transcription factor to the miR-203a-3p gene promoter, thereby upregulating miR-203a-3p expression. Further, increased miR-203a-3p was found to maintain neuropathic pain by targeting proprotein convertase 1, an endopeptidase necessary for the cleavage of proopiomelanocortin, the precursor of β-EP. The identified mechanism may provide an avenue for the development of new therapeutic targets for neuropathic pain treatment.

Abstract Background Adipokines, including adiponectin, are implicated in nociceptive pain; however, the underlying cellular and molecular mechanisms remain unknown. Methods Using electrophysiological recording, immunostaining, molecular biological approaches and animal behaviour tests, we elucidated a pivotal role of adiponectin in regulating membrane excitability and pain sensitivity by manipulating Cav3.2 channels in trigeminal ganglion (TG) neurons. Results Adiponectin enhanced T-type Ca2+ channel currents (I T) in TG neurons through the activation of adiponectin receptor 1 (adipoR1) but independently of heterotrimeric G protein-mediated signaling. Coimmunoprecipitation revealed a physical association between AdipoR1 and casein kinase II alpha-subunits (CK2α) in the TG, and inhibiting CK2 activity by chemical inhibitor or siRNA targeting CK2α prevented the adiponectin-induced I T response. Adiponectin significantly activated protein kinase C (PKC), and this effect was abrogated by CK2α knockdown. Adiponectin increased the membrane abundance of PKC beta1 (PKCβ1). Blocking PKCβ1 pharmacologically or genetically abrogated the adiponectin-induced I T increase. In heterologous expression systems, activation of adipoR1 induced a selective enhancement of Cav3.2 channel currents, dependent on PKCβ1 signaling. Functionally, adiponectin increased TG neuronal excitability and induced mechanical pain hypersensitivity, both attenuated by T-type channel blockade. In a trigeminal neuralgia model induced by chronic constriction injury of infraorbital nerve, blockade of adipoR1 signaling suppressed mechanical allodynia, which was prevented by silencing Cav3.2. Conclusion Our study elucidates a novel signaling cascade wherein adiponectin stimulates TG Cav3.2 channels via adipoR1 coupled to a novel CK2α-dependent PKCβ1. This process induces neuronal hyperexcitability and pain hypersensitivity. Insight into adipoR-Cav3.2 signaling in sensory neurons provides attractive targets for pain treatment.

Abstract Background Trace amines, such as tyramine, are endogenous amino acid metabolites that have been hypothesized to promote headache. However, the underlying cellular and molecular mechanisms remain unknown. Methods Using patch-clamp recording, immunostaining, molecular biological approaches and behaviour tests, we elucidated a critically functional role of tyramine in regulating membrane excitability and pain sensitivity by manipulating Kv1.4 channels in trigeminal ganglion (TG) neurons. Results Application of tyramine to TG neurons decreased the A-type K+ current (I A) in a manner dependent on trace amine-associated receptor 1 (TAAR1). Either siRNA knockdown of Gαo or chemical inhibition of βγ subunit (Gβγ) signaling abrogated the response to tyramine. Antagonism of protein kinase C (PKC) prevented the tyramine-induced I A response, while inhibition of conventional PKC isoforms or protein kinase A elicited no such effect. Tyramine increased the membrane abundance of PKCθ in TG neurons, and either pharmacological or genetic inhibition of PKCθ blocked the TAAR1-mediated I A decrease. Furthermore, PKCθ-dependent I A suppression was mediated by Kv1.4 channels. Knockdown of Kv1.4 abrogated the TAAR1-induced I A decrease, neuronal hyperexcitability, and pain hypersensitivity. In a mouse model of migraine induced by electrical stimulation of the dura mater surrounding the superior sagittal sinus, blockade of TAAR1 signaling attenuated mechanical allodynia; this effect was occluded by lentiviral overexpression of Kv1.4 in TG neurons. Conclusion These results suggest that tyramine induces Kv1.4-mediated I A suppression through stimulation of TAAR1 coupled to the Gβγ-dependent PKCθ signaling cascade, thereby enhancing TG neuronal excitability and mechanical pain sensitivity. Insight into TAAR1 signaling in sensory neurons provides attractive targets for the treatment of headache disorders such as migraine.

Of all of the components in SARS-CoV-2 inactivated vaccines, nucleocapsid protein (N) is the most abundant and highly conserved protein. However, the function of N in these vaccines, especially its influence on the targeted spike protein’s response, remains unknown. In this study, the immunization of mice with the N protein alone was shown to reduce the viral load, alleviating pulmonary pathological lesions after challenge with the SARS-CoV-2 virus. In addition, co-immunization and pre-immunization with N were found to induce higher S-specific antibody titers rather than compromise them. Remarkably, the same trend was also observed when N was administered as the booster dose after whole inactivated virus vaccination. N-specific IFN-γ-secreting T cell response was detected in all groups and exhibited a certain relationship with S-specific IgG antibody improvements. Together, these data indicate that N has an independent role in vaccine-induced protection and improves the S-specific antibody response to inactivated vaccines, revealing that an interplay mechanism may exist in the immune responses to complex virus components.

Cotton fabric was modified with Na2EDTA using a hydrothermal method to introduce surface hydroxyl groups, and subsequent coordination of Fe(III) ions to produce an Na2EDTA modified cotton-fiber-Fe complex (Fe-EDTA-Cotton). After characterization by SEM and FTIR, Fe-EDTA-Cotton was used as a heterogeneous photocatalyst to reduce Cr(VI) and degrade Reactive Red 195 oxidatively, to evaluate its catalytic activity. The results indicated that high Na2EDTA and/or NaH2PO4 concentrations, and/or high hydrothermal temperature increased the carboxyl group content (QCOOH) of the cotton fiber; high Fe content and elevated temperature could enhance coordination. Fe-EDTA-Cotton had a significant photocatalytic function in reducing Cr(VI). Increasing the QFe value of the complex or stronger irradiation favored photocatalytic reduction of Cr(VI) species. Increasing the system's pH did not help the reduction reaction. Fe-EDTA-Cotton could also remove Cr(VI) and Reactive Red 195 simultaneously from aqueous solution, and showed strong photocatalytic capacity. The reduction or oxidation reaction could be regulated by changing Na2S2O8 concentration in the reaction system, which might provide a new way to treat wastewater containing organic pigments and Cr(VI) species. Highlight Hydrothermal process enhanced EDTA modification of cotton fabric.; EDTA-modified cotton fiber Fe complex was prepared.; Cr(VI) removal was improved by its synergistic effect.; Fe complexes can remove Cr (VI) and organic dyes from aqueous solution in one bath.; The work might provide a new way to purify the wastewater containing organic pigments and Cr (VI) species.;

ObjectiveThe coronavirus disease 2019 (COVID-19) vaccines are considered to be an effective way to prevent the spread of the infection. Our previous study has shown that about 75% of healthcare workers (HCWs) in China were willing to receive the vaccine when it became available. Here, we examined the acceptance of a third booster dose among Chinese people and identified the influencing factors.MethodsA cross-sectional online survey was conducted and the snowball sampling method was utilized. An online questionnaire was provided to all the participants in the form of a quick response (QR) code. The questionnaire included general demographic information, views on vaccines, the General Health Questionnaire-12 (GHQ-12), and the Depression, Anxiety, and Stress Scale-21 (DASS-21). The univariate analysis was done between all the variables and our dependent variable. Then, we used the multivariate logistic regression model to examine the influencing factors of the third booster dose acceptance.ResultsWe collected 1,062 complete answers. Of these, 90.39% (n = 960) declared that they would accept the booster dose. Knowing more about the vaccine and recognizing the efficacy of vaccines were significantly associated with greater acceptance of the booster dose. People willing to take the booster dose had better psychological health. A belief that the booster dose could prevent severe infection caused by COVID-19 and enhance the effectiveness of the first two doses were the main contributing factors to vaccine acceptance. Vaccine hesitancy was mainly due to a low perceived risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and rapid mutation of SARS-CoV-2.ConclusionThis study revealed that Chinese people were very receptive to the third booster dose, which is an inspiring result. More positive attitudes regarding COVID-19 vaccination were supported by its efficacy and few side effects.

We established a model based on the “Malmquist index” to evaluate the dynamic performance of scientific and technological innovation in seven Chinese universities, which included five categories: changes in pure technical efficiency, changes in production technology, changes in scale efficiency, changes in organizational management performance, and changes in comprehensive efficiency. Seven domestic first-class universities were studied, and empirical analysis was performed based on data related to their scientific and technological innovation during three time periods (2013-2014, 2014-2015, and 2015-2016). Our results demonstrated that the contribution rate for each index was different for each university across the three time periods, and that Chinese universities is gradually transitioning from resource allocation to technical efficiency. In this paper, we explored the transformation from effect to efficiency and static to dynamic in the evaluation of the scientific and technological output of colleges and universities, and constructed systematic and unique multi-evaluation system for the scientific and technological output of universities.

Green plants provide food, energy and oxygen sources for human beings and animals on Earth through photosynthesis, which is essential to maintain regional ecological balance. However, few studies have focused on the natural oxygen supply capacity of urban green spaces. As a companion to photosynthesis in leaves, solar-induced chlorophyll fluorescence (SIF) contains abundant photosynthetic information. Currently, satellite-based SIF observations are considered to be a rapid and nondestructive ‘indicator’ of plant photosynthesis, which provides an alternative way to quantitatively assess the spatio-temporal dynamics of oxygen supply capacity in urban green spaces. This study examined the spatial patterns, long-term trends, and environmental control factors of SIF in the nine central cities in China from 2001 to 2020 based on the time-series of the global reconstructed GOSIF-v2 SIF dataset. The results were as follows: (1) There was a contrasting spatial difference between southern and northern cities in China, and multi-year mean SIF values of the southern cities were generally higher than those of the northern cities; (2) The interannual dynamics of SIF in each city generally showed an upward trend, with fluctuations, and the intraannual seasonal differences were more significant in northern cities than those in the southern cities; (3) The spatial trend analysis showed that Beijing, Guangzhou, and Chongqing have had the most significant improvements, followed by Xi’an, Wuhan, Chengdu, and Zhengzhou, while Tianjin and Shanghai have had the least improvements; and (4) The expansion of construction land has exerted significant impacts on the dynamics of the SIF trend in several cities, but it is not the only factor. All analyses indicated that the improvement of vegetation structure and function in the area can offset its negative effect.

Soil salinity is a widespread stress in semi-arid forests worldwide, but how to manage nitrogen (N) nutrition to improve plant saline tolerance remains unclear. Here, the cuttings of a widely distributed poplar from central Asia, Populus russikki Jabl., were exposed to either normal or low nitrogen (LN) concentrations for two weeks in semi-controlled greenhouse, and then they were added with moderate salt solution or not for another two weeks to evaluate their physiological, biochemical, metabolites and transcriptomic profile changes. LN-pretreating alleviated the toxicity caused by the subsequent salt stress in the poplar plants, demonstrated by a significant reduction in the influx of Na+ and Cl- and improvement of the K+/Na+ ratio. The other salt-stressed traits were also ameliarated, indicated by the variations of chlorophyll content, PSII photochemical activity and lipid peroxidation. Stress alleviation resulted from two different processes. First, LN pretreatment caused a significant increase of non-structural carbohydrates (NSC), allowed for an increased production of osmolytes and a higher potential fueling ion transport under subsequent salt condition, along with increased transcript levels of the cation/H+ ATPase. Second, LN pretreatment enhanced the transcript levels of stress signaling components and phytohormones pathway as well as antioxidant enzyme activities. The results indicate that early restrictions of N supply could enhance posterior survival under saline stress in poplar plants, which is important for plantation programs and restoration activities in semi-arid areas.

Objective To compare the outcomes of patients with non-traumatic cardiac arrest (CA) who received early versus late mechanical cardiopulmonary resuscitation (CPR) with the Lund University Cardiac Assist System (LUCAS) device in the emergency department (ED). Methods This was a retrospective observational study in the ED of a single medical center performed from May 2018 to December 2019; 68 patients with CA were eligible. We grouped the patients according to the time to initiating LUCAS use after CA into an early group (≤4 minutes) and late group (>4 minutes). Results The rate of return of spontaneous circulation (ROSC) was higher in the early group vs the late group (69.2% vs 52.4%, respectively). The 4-hour survival rate was significantly higher in the early group vs the late group (83.3% vs 45.5%, respectively), and CPR duration was significantly shorter in the early group (23.3 ± 12.5 vs 31.1 ± 14.8 minutes, respectively). Conclusion Early mechanical CPR can improve the success of achieving ROSC and the 4-hour survival rate in patients with non-traumatic CA in the ED, considering that more benefits were observed in patients who received early vs late LUCAS device therapy.

Objective: The Coronavirus disease 2019 (COVID-19) vaccine is currently available. This timely survey was conducted to provide insight into on the willingness of healthcare workers (HCWs)to receive the vaccine and determine the influencing factors.Methods: This was a cross-sectional online survey. An online questionnaire was provided to all participants and they were asked if they would accept a free vaccine. The questionnaire gathered general demographic information, and included the General Health Questionnaire (GHQ-12); Myers-Briggs Type Indicator questionnaire (MBTI); Depression, Anxiety, and Stress Scales (DASS-21); and the 12-item Short Form Health Survey (SF-12). The data were collected automatically and electronically. Univariate analysis was done between all the variables and our dependent variable. Multivariable logistic regression models were employed to examine and identify the associations between the acceptance of the COVID-19 vaccine with the associated variables.Results: We collected 505 complete answers. The participants included 269 nurses (53.27%), 206 clinicians (40.79%), 15 administrative staff (2.97%), and 15 other staff (2.97%). Of these, 76.63% declared they would accept the vaccine. The major barriers were concerns about safety, effectiveness, and the rapid mutation in the virus. Moreover, four factors were significantly associated with the willingness to receive the vaccine: (a) “understanding of the vaccine” (odds ratio (OR):2.322; 95% confidence interval [CI]: 1.355 to 3.979); (b) “worried about experiencing COVID-19” (OR 1.987; 95% CI: 1.197–3.298); (c) “flu vaccination in 2020” (OR 4.730; 95% CI: 2.285 to 9.794); and (d) “living with elderly individuals” (OR 1.928; 95% CI: 1.074–3.462).Conclusions: During the vaccination period, there was still hesitation in receiving the vaccine. The results will provide a rationale for the design of future vaccination campaigns and education efforts concerning the vaccine.

Abstract Background Migraine is a debilitating neurological disorder involving abnormal trigeminovascular activation and sensitization. However, the underlying cellular and molecular mechanisms remain unclear. Methods A rat model of conscious migraine was established through the electrical stimulation (ES) of the dural mater surrounding the superior sagittal sinus. Using patch clamp recording, immunofluorescent labelling, enzyme-linked immunosorbent assays and western blot analysis, we studied the effects of ES on sensory neuronal excitability and elucidated the underlying mechanisms mediated by voltage-gated ion channels. Results The calcitonin gene-related peptide (CGRP) level in the jugular vein blood and the number of CGRP-positive neurons in the trigeminal ganglia (TGs) were significantly increased in rats with ES-induced migraine. The application of ES increased actional potential firing in both small-sized IB4-negative (IB4 −) and IB4 + TG neurons. No significant changes in voltage-gated Na+ currents were observed in the ES-treated groups. ES robustly suppressed the transient outward K+ current (I A) in both types of TG neurons, while the delayed rectifier K+ current remained unchanged. Immunoblot analysis revealed that the protein expression of Kv4.3 was significantly decreased in the ES-treated groups, while Kv1.4 remained unaffected. Interestingly, ES increased the P/Q-type and T-type Ca2+ currents in small-sized IB4 − TG neurons, while there were no significant changes in the IB4 + subpopulation of neurons. Conclusion These results suggest that ES decreases the I A in small-sized TG neurons and increases P/Q- and T-type Ca2+ currents in the IB4 − subpopulation of TG neurons, which might contribute to neuronal hyperexcitability in a rat model of ES-induced migraine.

Introduction Large artery intracranial occlusive disease including middle cerebral artery (MCA) is a major contributor to the incidence of stroke in China. The data on the prognosis of symptomatic atherosclerotic MCA occlusions (MCAO) are limited. We aimed to investigate the related factors of unfavorable outcomes in patients with stroke associated with MCAO. Material and methods A total of 119 patients with MCAO symptom were enrolled in this retrospective longitudinal cohort study. All patients met inclusion criteria of cerebral angiography by CT angiography or magnetic resonance angiography. Stroke severity was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Results We showed an average follow-up time of 46.8 months, within which 20 (19.6%) cases died and 14 (13.7%) cases had stroke recurrence. Using mRS as an evaluation index, the patients were divided into an unfavourable outcome group (mRS > 2, 48 cases) and a favourable outcome group (mRS ≤ 2, 54 cases). Logistic regression analysis suggests that age and NIHSS score were independent risk factors for a poor outcome value. Coexisting other cerebral vascular occlusion was an independent risk factor for stroke recurrence. Age was an independent risk factor for death. Conclusions The prognosis of patients with MCAO was generally optimistic, with higher survival rate and longer survival time. As compared, elder age and higher NIHSS score both tend to be associated with worse prognosis of survival. MCAO patients with other extracranial or intracranial vascular occlusion have higher risk of recurrent stroke. Death rate increases with age among the MCAO patients.

Abstract Background Cholecystokinin (CCK) is implicated in the regulation of nociceptive sensitivity of primary afferent neurons. Nevertheless, the underlying cellular and molecular mechanisms remain unknown. Methods Using patch clamp recording, western blot analysis, immunofluorescent labelling, enzyme-linked immunosorbent assays, adenovirus-mediated shRNA knockdown and animal behaviour tests, we studied the effects of CCK-8 on the sensory neuronal excitability and peripheral pain sensitivity mediated by A-type K+ channels. Results CCK-8 reversibly and concentration-dependently decreased A-type K+ channel (I A) in small-sized dorsal root ganglion (DRG) neurons through the activation of CCK type B receptor (CCK-BR), while the sustained delayed rectifier K+ current was unaffected. The intracellular subunit of CCK-BR coimmunoprecipitated with Gαo. Blocking G-protein signaling with pertussis toxin or by the intracellular application of anti-Gβ antibody reversed the inhibitory effects of CCK-8. Antagonism of phosphatidylinositol 3-kinase (PI3K) but not of its common downstream target Akts abolished the CCK-BR-mediated I A response. CCK-8 application significantly activated JNK mitogen-activated protein kinase. Antagonism of either JNK or c-Src prevented the CCK-BR-mediated I A decrease, whereas c-Src inhibition attenuated the CCK-8-induced p-JNK activation. Application of CCK-8 enhanced the action potential firing rate of DRG neurons and elicited mechanical and thermal pain hypersensitivity in mice. These effects were mediated by CCK-BR and were occluded by I A blockade. Conclusion Our findings indicate that CCK-8 attenuated I A through CCK-BR that is coupled to the Gβγ-dependent PI3K and c-Src-mediated JNK pathways, thereby enhancing the sensory neuronal excitability in DRG neurons and peripheral pain sensitivity in mice.

Aminoglycoside antibiotics, such as gentamicin, are known to have vestibulotoxic effects, including ataxia and disequilibrium. To date, however, the underlying cellular and molecular mechanisms are still unclear. In this study, we determined the role of gentamicin in regulating the sustained delayed rectifier K+ current (IDR) and membrane excitability in vestibular ganglion (VG) neurons in mice. Our results showed that the application of gentamicin to VG neurons decreased the IDR in a concentration-dependent manner, while the transient outward A-type K+ current (IA) remained unaffected. The decrease in IDR induced by gentamicin was independent of G-protein activity and led to a hyperpolarizing shift of the inactivation Vhalf. The analysis of phospho-c-Jun N-terminal kinase (p-JNK) revealed that gentamicin significantly stimulated JNK, while p-ERK and p-p38 remained unaffected. Blocking Kv1 channels with α-dendrotoxin or pretreating VG neurons with the JNK inhibitor II abrogated the gentamicin-induced decrease in IDR. Antagonism of JNK signaling attenuated the gentamicin-induced stimulation of PKA activity, whereas PKA inhibition prevented the IDR response induced by gentamicin. Moreover, gentamicin significantly increased the number of action potentials fired in both phasic and tonic firing type neurons; pretreating VG neurons with the JNK inhibitor II and the blockade of the IDR abolished this effect. Taken together, our results demonstrate that gentamicin decreases the IDR through a G-protein-independent but JNK and PKA-mediated signaling pathways. This gentamicin-induced IDR response mediates VG neuronal hyperexcitability and might contribute to its pharmacological vestibular effects.

Abstract Background As an important biofuel plant, the demand for higher yield Jatropha curcas L. is rapidly increasing. However, genetic analysis of Jatropha and molecular breeding for higher yield have been hampered by the limited number of molecular markers available. Results An ultrahigh-density linkage map for a Jatropha mapping population of 153 individuals was constructed and covered 1380.58 cM of the Jatropha genome, with average marker density of 0.403 cM. The genetic linkage map consisted of 3422 SNP and indel markers, which clustered into 11 linkage groups. With this map, 13 repeatable QTLs (reQTLs) for fruit yield traits were identified. Ten reQTLs, qNF-1, qNF-2a, qNF-2b, qNF-2c, qNF-3, qNF-4, qNF-6, qNF-7a, qNF-7b and qNF-8, that control the number of fruits (NF) mapped to LGs 1, 2, 3, 4, 6, 7 and 8, whereas three reQTLs, qTWF-1, qTWF-2 and qTWF-3, that control the total weight of fruits (TWF) mapped to LGs 1, 2 and 3, respectively. It is interesting that there are two candidate critical genes, which may regulate Jatropha fruit yield. We also identified three pleiotropic reQTL pairs associated with both the NF and TWF traits. Conclusion This study is the first to report an ultrahigh-density Jatropha genetic linkage map construction, and the markers used in this study showed great potential for QTL mapping. Thirteen fruit-yield reQTLs and two important candidate genes were identified based on this linkage map. This genetic linkage map will be a useful tool for the localization of other economically important QTLs and candidate genes for Jatropha.

Abstract Objective This study aimed to reveal the mitochondrial genomes (mtgenomes) of Tetrix japonica and Alulatettix yunnanensis, and the phylogenetics of Orthoptera species. Methods The mtgenomes of A. yunnanensis and T. japonica were firstly sequenced and assembled through partial sequences amplification, and then the genome organization and gene arrangement were analyzed. Based on nucleotide/amino acid sequences of 13 protein-coding genes and whole mtgenomes, phylogenetic trees were established on 37 Orthoptera species and 5 outgroups, respectively. Results Except for a regulation region (A+T rich region), a total of 37 genes were found in mtgenomes of T. japonica and A. yunnanensis, including 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes, which exhibited similar characters with other Orthoptera species. Phylogenetic tree based on 13 concatenated protein-coding nucleotide sequences were considered to be more suitable for phylogenetic reconstruction of Orthoptera species than amino acid sequences and mtgenomes. The phylogenetic relationships of Caelifera species were Acridoidea and Pamphagoidea > Pyrgomorphoidea > Pneumoroidea > Eumastacoidea > Tetrigoidea > Tridactyloidea. Besides, a sister-group relationship between Tettigonioidea and Rhaphidophoroidea was revealed in Ensifera. Conclusion Concatenated protein-coding nucleotide sequences of 13 genes were suitable for reconstruction of phylogenetic relationship in orthopteroid species. Tridactyloidea was a sister group of Tetrigoidea in Caelifera, and Rhaphidophoroidea was a sister group of Tettigonioidea in Ensifera.

As an indispensable part of Internet of Things (IoT), wireless sensor networks (WSNs) are more and more widely used with the rapid development of IoT. The neighbor discovery protocols are the premise of communication between nodes and networking in energy-limited self-organizing wireless networks, and play an important role in WSNs. Because the node energy is limited, neighbor discovery must operate in an energy-efficient manner, that is, under the condition of a given energy budget, the neighbor discovery performance should be as good as possible, such that the discovery latency would be as small as possible and the discovered neighbor percentage as large as possible. The indirect neighbor discovery mainly uses the information of the neighbors that have been found by a pairwise discovery method to more efficiently make a re-planning of the discovery wake-up schedules of the original pairwise neighbor discovery, thereby improving the discovery energy efficiency. The current indirect neighbor discovery methods are mainly divided into two categories: one involves removing the inefficient active slots in the original discovery wake-up schedules, and the other involves adding some efficient active slots. However, the two categories of methods have their own limitations. The former does not consider that this removal operation destroys the integrity of the original discovery wake-up schedules and hence the possibility of discovering new neighbors is reduced, which adversely affects the discovered neighbor percentage. For the latter category, there are still inefficient active slots that were not removed in the re-planned wake-up schedules. The motivation of this paper is to combine the advantages of these two types of indirect neighbor discovery methods, that is, to combine the addition of efficient active slots and the removal of inefficient active slots. To achieve this goal, this paper proposes, for the first time, the concept of virtual nodes in neighbor discovery to maximize the integrity of the original wake-up schedules and achieve the goals of adding efficient active slots and removing inefficient active slots. Specifically, a virtual node is a collaborative group that is formed by nodes within a small range. The nodes in a collaborative group share responsibility for the activating task of one member node, and the combination of these nodes’ wake-up schedules forms the full wake-up schedule of a node that only uses a pairwise method. In addition, this paper proposes a set of efficient group management mechanisms, and the key steps affecting energy efficiency are analyzed theoretically to obtain the energy-optimal parameters. The extended simulation experiments in multiple scenarios show that, compared with other methods, our neighbor discovery protocol based on virtual nodes (VN-NDP) has a significant improvement in average discovery delay and discovered neighbor percentage performance at a given energy budget. Compared with the typical indirect neighbor discovery algorithm EQS, a neighbor discovery with extended quorum system, our proposed VN-NDP method reduces the average discovery delay by up to 10.03 % and increases the discovered neighbor percentage by up to 18.35 % .

The aim of this study was to investigate the impact of Lycium barbarum leaves flavonoids (LBLF) on lipid accumulation in normal and oleic acid-induced HepG2 cells. The experiment was divided into six groups as follows: blank, model, positive control, low-, medium-, and high-dose LBLF. Oil red O staining was performed to assess the aggregation of lipid droplets in each group, and lipid levels and oxidative stress indicators were measured. Finally, real-time polymerase chain reaction (real-time PCR) and Western blot were used to detect the expression of mRNAs and proteins associated with lipid synthesis. The results indicated that LBLF could decrease the increase in the levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA) and reactive oxygen species (ROS) induced by oleic acid in HepG2 cells. It also could increase high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD), glutathione, and catalase levels. Additionally, Western blot results suggested that LBLF intervention could up-regulate phosphorylated adenosine 5’-monophosphate (AMP)-activated protein kinase (p-AMPK) and AMPK levels, and down-regulate the protein expression of sterol regulatory element-binding protein 1c(SREBP-1c), peroxisome proliferator-activated receptor γ (PPARγ), and CCAAT enhancer binding protein alpha (CEBPα). Real-time PCR results indicated that LBLF intervention down-regulated the expression of genes such as ACC, FAS, SREBP-1c, SCD-1, PPARγ, and CEBPα. In conclusion, LBLF could partially alleviate lipid metabolism disorder in oleic acid-induced HepG2 cells by regulating the expression levels of lipid synthesis and oxidation-related genes.

Previous research has shown that the geographical distribution patterns of freshwater fishes and amphibians have been influenced by past climatic oscillations in China resulting from Pleistocene glacial activity. However, it remains unknown how these past changes have impacted the present-day distribution of Chinese freshwater crabs. This work describes the diversity and endemism of freshwater crabs belonging to Sinopotamon, a highly speciose genus endemic to China, and evaluates its distribution in terms of topography and past climatic fluctuations. Species diversity within Sinopotamon was found to be concentrated in an area from the northeastern edge of the Yunnan-Guizhou Plateau to the Jiangnan Hills, and three areas of endemism were identified. Multiple regression analysis between current climatic variables and Sinopotamon diversity suggested that regional annual precipitation, minimum temperature in the coldest month, and annual temperature range significantly influenced species diversity and may explain the diversity patterns of Sinopotamon. A comparison of ecological niche models (ENMs) between current conditions and the last glacial maximum (LGM) showed that suitable habitat for Sinopotamon in China severely contracted during the LGM. The coincidence of ENMs and the areas of endemism indicated that southeast of the Daba Mountains, and central and southeastern China, are potential Pleistocene refuges for Sinopotamon. The presence of multiple Pleistocene refuges within the range of this genus could further promote inter- and intraspecific differentiations, and may have led to high Sinopotamon species diversity, a high endemism rate and widespread distribution.

The N6-methyladenosine (m6A) modification of RNA is an emerging epigenetic regulatory mechanism that has been shown to participate in various pathophysiological processes. However, its involvement in modulating neuropathic pain is still poorly understood. In this study, we elucidate a functional role of the m6A demethylase alkylation repair homolog 5 (ALKBH5) in modulating trigeminal-mediated neuropathic pain. Peripheral nerve injury selectively upregulated the expression level of ALKBH5 in the injured trigeminal ganglion (TG) of rats. Blocking this upregulation in injured TGs alleviated trigeminal neuropathic pain, while mimicking the upregulation of ALKBH5 in intact TG neurons sufficiently induced pain-related behaviors. Mechanistically, histone deacetylase 11 downregulation induced by nerve injury increases histone H3 lysine 27 acetylation (H3K27ac), facilitating the binding of the transcription factor forkhead box protein D3 (FOXD3) to the Alkbh5 promoter and promoting Alkbh5 transcription. The increased ALKBH5 erases m6A sites in Htr3a messenger RNA (mRNA), resulting in an inability of YT521-B homology domain 2 (YTHDF2) to bind to Htr3a mRNA, thus causing an increase in 5-HT3A protein expression and 5-HT3 channel currents. Conversely, blocking the increased expression of ALKBH5 in the injured TG destabilizes nerve injury–induced 5-HT3A upregulation and reverses mechanical allodynia, and the effect can be blocked by 5-HT3A knockdown. Together, FOXD3-mediated transactivation of ALKBH5 promotes neuropathic pain through m6A-dependent stabilization of Htr3a mRNA in TG neurons. This mechanistic understanding may advance the discovery of new therapeutic targets for neuropathic pain management. [ABSTRACT FROM AUTHOR]

Because flexible robots have flexible components such as reducers, there are problems of accuracy deviation and end vibration in the process of external interference and trajectory tracking. This leads to the proposal of a Sliding Mode Control Approach Based on RBF Neural Network (SMC-RBF) parameter optimization. This method is mainly applied to reduce the end vibration and running position error of flexible robot. Firstly, the Newton-Euler method is used to establish the dynamic model of robot considering joint flexibility. At the same time, the experiment optimizes the Sliding Mode Control (SMC) method through RBF neural network. The experiments verify the control methods of the two-joint flexible robot and the six-joint flexible robot respectively. In the control of two-joint robot, the maximum tracking curve error of SMC is only about 0.25 rad under the interference of pulse signal; And the recovery time is only about 1 s. In the control of 6-joint robot, the maximum error of RBF-sliding mode control method on XYZ axis is 0.7 mm, 0.25 mm and 1.25 mm respectively; The error on three axes is smaller than that of traditional PD control method. The results demonstrate that the tracking error of the improved mode control is small, the chattering phenomenon of the robot system is weakened as well. [ABSTRACT FROM AUTHOR]