Nicotinamide mononucleotide (NMN), an important transforming precursor of nicotinamide adenine dinucleotide (NAD+). Numerous studies have confirmed the neuroprotective effects of NMN in nervous ...system diseases. However, its role in spinal cord injury (SCI) and the molecular mechanisms involved have yet to be fully elucidated.
We established a moderate-to-severe model of SCI by contusion (70 kdyn) using a spinal cord impactor. The drug was administered immediately after surgery, and mice were intraperitoneally injected with either NMN (500 mg NMN/kg body weight per day) or an equivalent volume of saline for seven days. The central area of the spinal cord was harvested seven days after injury for the systematic analysis of global gene expression by RNA Sequencing (RNA-seq) and finally validated using qRT-PCR.
NMN supplementation restored NAD+ levels after SCI, promoted motor function recovery, and alleviated pain. This could potentially be associated with alterations in NAD+ dependent enzyme levels. RNA sequencing (RNA-seq) revealed that NMN can inhibit inflammation and potentially regulate signaling pathways, including interleukin-17 (IL-17), tumor necrosis factor (TNF), toll-like receptor, nod-like receptor, and chemokine signaling pathways. In addition, the construction of a protein-protein interaction (PPI) network and the screening of core genes showed that interleukin 1β (IL-1β), interferon regulatory factor 7 (IRF 7), C-X-C motif chemokine ligand 10 (Cxcl10), and other inflammationrelated factors, changed significantly after NMN treatment. qRT-PCR confirmed the inhibitory effect of NMN on inflammatory factors (IL-1β, TNF-α, IL-17A, IRF7) and chemokines (chemokine ligand 3, Cxcl10) in mice following SCI.
The reduction of NAD+ levels after SCI can be compensated by NMN supplementation, which can significantly restore motor function and relieve pain in a mouse model. RNA-seq and qRT-PCR systematically revealed that NMN affected inflammation-related signaling pathways, including the IL-17, TNF, Toll-like receptor, NOD-like receptor and chemokine signaling pathways, by down-regulating the expression of inflammatory factors and chemokines.
Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Massive internal migration from rural to urban areas poses new challenges for leprosy control in Shanghai, China. This ...retrospective epidemiological study examined new cases of leprosy diagnosed in Shanghai from 2000 to 2019, with emphasis on internal migration cases. There were 145 cases of leprosy in the study period; the majority of cases (89.0%) were internal migrants. Migrant cases had a mean of 25.4 months lag time from onset of symptoms to diagnosis, which was significantly longer than that of resident cases (mean 10.8 months, p < 0.001). Greater lag time from the first visit to diagnosis was observed in migrant cases (mean 23.2 months) compared with resident cases (mean 9.4 months, p < 0.001). A large majority of cases (91.0%) had been misdiagnosed. Internal migrant cases were responsible for most incidences of leprosy in Shanghai. They often did not receive timely diagnosis and treatment, which may have an adverse impact on the prevention of epidemic leprosy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Fossil energy is the material basis of human survival, economic development and social progress. The relationship between energy consumption and economic growth is becoming increasingly close. ...However, energy consumption is the major source of greenhouse gases, which can significantly affect the balance of the global ecosystem. It has become the common goal of countries worldwide to address climate change, reduce carbon dioxide emissions, and implement sustainable development strategies. In this study, we applied an approximate relationship analysis, a decoupling relationship analysis, and a trend analysis to explore the relationship between energy consumption and economic growth using data from Kazakhstan for the period of 1993-2010. The results demonstrated： （1） the total energy consumption and GDP in Kazakhstan showed a ＂U＂-type curve from 1993 to 2010. This curve was observed because 1993-1999 was a period during which Kazakhstan transitioned from a republic to an independent country and experienced a difficult transition from a planned to a market economy. Then, the economic system became more stable and the industrial production increased rapidly because of the effective financial, monetary and industrial policy support from 2000 to 2010. （2） The relationships between energy con- sumption and carbon emissions, economic growth and energy exports were linked; the carbon emissions were mainly derived from energy consumption, and the dependence of economic growth on energy exports gradually increased from 1993 to 2010. Before 2000, the relationship between energy consumption and economic growth was in a recessional decoupling state because of the economic recession. After 2000, this relationship was in strong and weak decoupling states because the international crude oil prices rose and energy exports increased greatly year by year. （3） It is forecasted that Kazakhstan cannot achieve its goal of energy consumption by 2020. Therefore, a low-carbon economy is the best strategic choice to address climate change from a global perspective in Kazakhstan. Thus, we proposed strategies including the improvement of the energy consumption structure, the development of new energy and renewable energy, the use of cleaner production technologies, the adjustment and optimization of the industrial structure, and the expansion of forest areas.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective
This study investigated how the injury completeness, level, and duration of spinal cord injury (SCI) affect cortical morphometric changes in humans.
Methods
T1‐weighted images were acquired ...from 59 SCI patients and 37 healthy controls. Voxel‐based morphometry analyses of the gray matter volume (GMV) were performed between SCI patients and healthy controls, complete SCI and incomplete SCI, and tetraplegia and paraplegia. Correlation analyses were performed to explore the associations between GMV and clinical variables in SCI patients.
Results
Compared to healthy controls, SCI patients showed decreased GMV in bilateral middle frontal gyrus, left superior frontal gyrus (SFG), left medial frontal gyrus in the whole‐brain analysis, while increased GMV in right supplementary motor area and right pallidum in ROI analysis. The complete SCI had lower GMV in left primary somatosensory cortex (S1) and higher GMV in left primary motor cortex compared with incomplete SCI. Lower GMV was identified in left thalamus and SFG in tetraplegia than that in paraplegia. Moreover, time since injury was positive with the GMV in right pallidum, positive correlations were observed between the GMV in bilateral S1 and total motor and sensory scores, whereas the GMV in left cuneus was negatively correlated with total motor and sensory scores in SCI patients.
Conclusions
The study provided imaging evidence for identifying cerebral structural abnormalities in SCI patients and significant differences in complete/incomplete and paraplegia/tetraplegia subgroups. These results suggested brain structural changes occur after SCI and these changes may depend on the injury completeness, level, and duration.
Our study provided imaging evidence for identifying cerebral structural abnormalities in patients with SCI and significant differences in complete/incomplete and paraplegia/tetraplegia subgroups.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Uyghur food culture has a long history. It is rich in resources, with the strong characteristics of being "green" and healthy, and having high nutritional value. We analyze the development and ...current status of Uyghur food culture, and explore the value of developing this food culture's resources. Traditional Uyghur food culture formed with influences from many ethnic groups, and has evolved into an intangible element of cultural heritage. It has several components with different healthy and therapeutic functions and is widely utilized in local communities. Overall, Uyghur food is rich in nutrients and beneficial for health. We propose strategies to address issues associated with Uyghur food culture and cultural resources, and specific measures for the development of these resources.
Cervical spine injury (CSI) accounts for significant mortality in the intensive care unit (ICU), whereas sepsis remains one of the major causes of death in patients with CSI. However, there is no ...effective method to diagnose sepsis timely. The aim of this study is to investigate the effect of metagenomic next-generation sequencing (mNGS) on the pathogen features and the prognostic prediction of CSI patients with sepsis. A total of 27 blood samples from 17 included patients were tested by mNGS. Data of mNGS were compared with the conventional culture method. The Kaplan–Meier plots were used to visualize survival curves. A Cox proportional hazards model was used to identify independent prognostic factors for survival. Results showed that mNGS detected a wide spectrum of pathogens in CSI patients with sepsis, including 129 bacterial species, 8 viral species, and 51 fungal species. mNGS indicated 85.2% positive results, while the conventional culture method only showed 11.1% positive results in the blood samples. Further analyses revealed that mNGS had no prognostic effect on the septic CSI patients in ICU, whereas positive results of blood culture were closely correlated with an increased hazard ratio (HR) (HR 77.7067, 95%CI 2.860–2641.4595,
p
= 0.0155). Our results suggested that the mNGS application may provide evidence for clinicians to use antibiotics when a CSI case is diagnosed with sepsis.
The persistence of Mycobacterium leprae (M. leprae) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune ...responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions.
Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha) and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg) cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma) expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings.
Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Spinal cord injury (SCI) can reshape gut microbial composition, significantly affecting clinical outcomes in SCI patients. However, mechanisms regarding gut-brain interactions and their clinical ...implications have not been elucidated. We hypothesized that short-chain fatty acids (SCFAs), intestinal microbial bioactive metabolites, may significantly affect the gut-brain axis and enhance functional recovery in a mouse model of SCI. We enrolled 59 SCI patients and 27 healthy control subjects and collected samples. Thereafter, gut microbiota and SCFAs were analyzed using 16 S rDNA sequencing and gas chromatography-mass spectrometry, respectively. We observed an increase in Actinobacteriota abundance and a decrease in Firmicutes abundance. Particularly, the SCFA-producing genera, such as Faecalibacterium, Megamonas, and Agathobacter were significantly downregulated among SCI patients compared to healthy controls. Moreover, SCI induced downregulation of acetic acid (AA), propionic acid (PA), and butyric acid (BA) in the SCI group. Fecal SCFA contents were altered in SCI patients with different injury course and injury segments. Main SCFAs (AA, BA, and PA) were administered in combination to treat SCI mice. SCFA supplementation significantly improved locomotor recovery in SCI mice, enhanced neuronal survival, promoted axonal formation, reduced astrogliosis, and suppressed microglial activation. Furthermore, SCFA supplementation downregulated NF-κB signaling while upregulating neurotrophin-3 expression following SCI. Microbial sequencing and metabolomics analysis showed that SCI patients exhibited a lower level of certain SCFAs and related bacterial strains than healthy controls. SCFA supplementation can reduce inflammation and enhance nourishing elements, facilitating the restoration of neurological tissues and the improvement of functional recuperation. Trial registration: This study was registered in the China Clinical Trial Registry ( www.chictr.org.cn ) on February 13, 2017 (ChiCTR-RPC-17010621).
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