Different Types of Cell Death in Diabetic Neuropathy: A Focus on Mechanisms and Therapeutic Strategies.

Diabetic neuropathy (DN) is a common complication of diabetes, affecting over 50% of patients, leading to significant pain and a burden. Currently, there are no effective treatments available. Cell death is considered a key factor in promoting the progression of DN. This article reviews how cell death is initiated in DN, emphasizing the critical roles of oxidative stress, mitochondrial dysfunction, inflammation, endoplasmic reticulum stress, and autophagy. Additionally, we thoroughly summarize the mechanisms of cell death that may be involved in the pathogenesis of DN, including apoptosis, autophagy, pyroptosis, and ferroptosis, among others, as well as potential therapeutic targets offered by these death mechanisms. This provides potential pathways for the prevention and treatment of diabetic neuropathy in the future.

MiR-10b-5p Regulates Neuronal Autophagy and Apoptosis Induced by Spinal Cord Injury Through UBR7.

This study aimed to explore the effects of miR-10b-5p on autophagy and apoptosis in neuronal cells after spinal cord injury (SCI) and the molecular mechanism. Bioinformatics was used to analyze the differentially expressed miRNAs. The expression of related genes and proteins were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. Cell proliferation was detected by 5-ethynyl-2'-deoxyuridine (EdU), and apoptosis was detected by flow cytometry or terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). Coimmunoprecipitation confirmed the interaction between UBR7 and Wnt1 or Beclin1. Autophagy was detected by the dansylcadaverine (MDC). The Basso Beattie Bresnahan (BBB) score was used to evaluate motor function, and hematoxylin-eosin (H&E) and Nissl staining were used to detect spinal cord tissue repair and neuronal changes. The result shows that the expression of miR-10b-5p was downregulated in the SCI models, and transfection of a miR-10b-5p mimic inhibited neuronal cell apoptosis. MiR-10b-5p negatively regulated the expression of UBR7, and the inhibitory effect of the miR-10b-5p mimic on neuronal cell apoptosis was reversed by overexpressing UBR7. In addition, UBR7 can regulate apoptosis by affecting the Wnt/ß-catenin pathway by promoting Wnt1 ubiquitination. Treatment with the miR-10b-5p mimic effectively improved motor function, inhibited neuronal cell apoptosis, and promoted spinal cord tissue repair in SCI rats. Overall, miR-10b-5p can alleviate SCI by downregulating UBR7 expression, inhibiting Wnt/ß-catenin signaling pathway ubiquitination to reduce neuronal apoptosis, or inhibiting Beclin 1 ubiquitination to promote autophagy.

Suppression of cerebral ischemia injury induced blood brain barrier breakdown by dexmedetomidine via promoting CCN1.

BACKGROUND: Blood-brain barrier (BBB) could aggravate cerebral ischemia injury. Dexmedetomidine (Dex) has been believed to play a protective role in cerebral ischemia injury-induced BBB injury. METHODS: Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD) models were established to simulate cerebral ischemia injury. Animal experiments included 4 groups, Sham, MCAO, MCAO+Dex, MCAO+Dex+sh-CCN1. Generally applicable gene set enrichment analysis was performed to analyze gene expression difference. Total collagen content and Evans blue staining were performed to measure infarct ratio and BBB breakdown, respectively. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and western blotting, respectively. The levels of IL-1ß, TNF-α, and IL-6 in serum were measured with commercial ELISA kits. RESULTS: Dex greatly promoted the expression level of CCN1. Dex suppressed cerebral ischemia injury, increased tight junction protein expression, improved the memory ability and neurological function of MCAO rats through targeting CCN1. The significant increase of inflammatory factors in the serum of MCAO rats were suppressed by Dex. Dex suppressed OGD induced increase of HRP permeability and promoting tight junction protein expression in vitro through regulating CCN1. The neurological function evaluation was performed with Neurological Severity Score (NSS) and Longa Score Scale. CONCLUSIONS: Dex could remarkably alleviate cerebral ischemia injury by inhibiting BBB breakdown, inflammatory response, and promoting neurological function and tight junction protein expression via up-regulating CCN1. This study might provide a novel therapeutic target for the prevention and treatment of cerebral ischemia injury-induced BBB.

P2Y13 receptor involved in HIV-1 gp120 induced neuropathy in superior cervical ganglia through NLRP3 inflammasome activation.

Cardiac autonomic neuropathy resulting from human immunodeficiency virus (HIV) infection is common; however, its mechanism remains unknown. The current work attempted to explore the function and mechanism of the P2Y13 receptor in HIV-glycoprotein 120 (gp120)-induced neuropathy in cervical sympathetic ganglion. The superior cervical ganglion (SCG) of the male SD rat was coated with HIV-gp120 to establish a model of autonomic neuropathy. In each group, we measured heart rate, blood pressure, heart rate variability, sympathetic nerve discharge and cardiac function. The expression of P2Y13 mRNA and protein in the SCG was tested by real-time polymerase chain reaction and western blotting. Additionally, this study focused on identifying the protein levels of NOD-like receptor family pyrin domain-containing 3 (NLRP3), Caspase-1, Gasdermin D (GSDMD), interleukin (IL)-1ß and IL-18 in the SCG using western blotting and immunofluorescence. In gp120 rats, increased blood pressure, heart rate, cardiac sympathetic nerve activity, P2Y13 receptor levels and decreased cardiac function could be found. P2Y13 shRNA or MRS2211 inhibited the above mentioned changes induced by gp120, suggesting that the P2Y13 receptor may be engaged in gp120-induced sympathetic nerve injury. Moreover, the levels of NLRP3, Caspase-1, GSDMD, IL-1ß and IL-18 in the gp120 group were increased, while significantly decreased by P2Y13 shRNA or MRS2211. Therefore, the P2Y13 receptor is involved in gp120-induced sympathetic neuropathy, and its molecular mechanism shows an association with the activation of the NLRP3 inflammasome, followed by GSDMD formation along with the release of inflammatory factors including IL-1ß and IL-18. This article is part of the Special Issue on "Purinergic Signaling: 50 years".

The potential role of CpG oligodeoxynucleotides on diabetic cardiac autonomic neuropathy mediated by P2Y12 receptor in rat stellate ganglia.

Cardiac autonomic neuropathy has a high prevalence in type 2 diabetes, which increases the risk of cardiovascular system disorders. CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) ligand, has been shown to have cardioprotection and cellular protection. Our previous work showed that P2Y12 in stellate ganglia (SG) is involved in the process of diabetic cardiac autonomic neuropathy (DCAN). Here, we aim to investigate whether CpG-ODN 1826 plays a protective role in DCAN and whether this beneficial protection involves regulation of the P2Y12-mediated cardiac sympathetic injury. Our results revealed that CpG-ODN 1826 activated TLR9 receptor, improved the abnormal blood pressure (BP), heart rate (HR), heart rate variability (HRV) and sympathetic nerve discharge (SND) activity in diabetic rats and reduced the up-regulated NF-κB, P2Y12 receptor, TNF-α and IL-1ß in SG. Meanwhile, CpG-ODN 1826 significantly decreased the elevated ATP, nuclear receptor coactivator 4 (NCOA4), iron, ROS and MDA levels and increased GPX4 and GSH levels. In addition, CpG-ODN 1826 contributes to maintain normalization of mitochondrial structure in SG. Overall, CpG-ODN 1826 alleviates the sympathetic excitation and abnormal neuron-glial signal communication via activating TLR9 receptors to achieve a balance of autonomic activity and relieve the DCAN in rats. The mechanism may involve the regulation of P2Y12 receptor in SG by reducing ATP release and NF-κB expression, which counteract neuroinflammation and ferroptosis mediated by activated P2Y12 in SG.

Mechanism of SET8 Activates the Nrf2-KEAP1-ARE Signaling Pathway to Promote the Recovery of Motor Function after Spinal Cord Injury.

Background: Spinal cord injury (SCI) is a common injury of the central nervous system (CNS), and astrocytes are relatively abundant glial cells in the CNS that impairs the recovery of motor function after SCI. It was confirmed that the oxidative stress of mitochondria leads to the accumulation of reactive oxygen species (ROS) in cells, which plays a key role in the motor function of astrocytes. However, the mechanism by which oxidative stress affects astrocyte motility after SCI is still unexplained. Therefore, this study investigated the influence of SET8-regulated oxidative stress on astrocyte autophagy levels after SCI in rats and the potential mechanisms of action. Methods: We used real-time quantitative PCR, western blotting, and immunohistochemical staining to analyze SET8, Keap1, and Nrf2 expression at the cellular level and in SCI tissues. ChIP to detect H4K20me1 enrichment in the Keap1 promoter region under OE-SET8 (overexpression of SET8) conditions. Western blotting was used to assess the expression of signature proteins of astrocytes, proteins associated with autophagy, proteins associated with glial scar formation, reactive oxygen species (ROS) levels in cells using DHE staining, and astrocyte number, morphological alterations, and induction of glial scar formation processes using immunofluorescence. In addition, the survival rate of neurons after SCI in rats was examined by using NiSSl staining. Results: OE-SET8 upregulates the enrichment of H4K20me1 in Keap1, inhibits Keap1 expression, activates the Nrf2-ARE signaling pathway to suppress ROS accumulation, inhibits oxidative stress-induced autophagy and glial scar formation in astrocytes, and leads to reduced neuronal loss, which promoted the recovery and improvement of motor function after SCI in rats. Conclusion: Overexpression of SET8 alleviated oxidative stress by regulating Keap1/Nrf2/ARE, inhibited astrocyte autophagy levels, and reduced glial scar formation as well as neuronal loss, thereby promoting improved recovery of motor function after SCI. Thus, the SET8/H4K20me1 regulatory function may be a promising cellular therapeutic intervention point after SCI.

Application of a preoperative pain management mode based on instant messaging software in elderly hip fracture patients: a randomized controlled trial.

BACKGROUND: Preoperative analgesia of hip fracture in elderly patients is important, but it is also lacking. In particular, nerve block was not provided in time. In order to provide more effective analgesia, we designed a multimodal pain management mode based on instant messaging software. METHODS: From May to September 2022, a total of 100 patients with unilateral hip fracture aged over 65 were randomly divided into the test group and the control group. Finally, 44 patients in each group completed the result analysis. A new pain management mode was used in the test group. This mode focuses on the full information exchange between medical personnel in different departments, early fascia iliaca compartment block (FICB), and closed-loop pain management. Outcomes include the time when FICB is completed for the first time; The number of cases of FICB completed by emergency doctors; Patients' pain score, pain duration. RESULTS: The time for patients in the test group to complete FICB for the first time was 3.0 [1.925-3.475] h, which was less than the time for patients in the control group (4.0 [3.300-5.275] h). The difference was statistically significant (P < 0.001). Compared with 16 patients in the control group, 24 patients in the test group completed FICB by emergency doctors, and there was no statistical difference between the two groups (P = 0.087). The test group was superior to the control group in the highest NRS score (4.00 [3.00-4.00] vs 5.00 [4.00-5.75]), the duration of the highest NRS score (20.00 [20.00-25.00] mins vs 40.00 [30.00-48.75] mins), and the NRS > 3 time (35.00 [20.00-45.00] mins vs 72.50 [60.00-45.00] mins). The analgesic satisfaction of patients in the test group (5.00 [4.00-5.00]) was also significantly higher than that of the control group (3.00 [3.00-4.00]). The above four indexes were different between the two groups (P < 0.001). CONCLUSIONS: Using instant messaging software, the new model of pain management can enable patients to receive FICB as soon as possible and improve the timeliness and effectiveness of analgesia. TRIAL REGISTRATION: Chinese Clinical Registry Center, ChiCTR2200059013, 23/04/2022.

Rectus sheath block versus local anesthetic infiltration in pediatric laparoscopic inguinal hernia repair: a randomized controlled trial.

BACKGROUND: Rectus sheath block (RSB) and local anesthetic infiltration (LAI) are used for postoperative analgesia in pediatric laparoscopic inguinal hernia repair. However, whether the analgesic effect of RSB is superior to LAI remains unclear. The authors hypothesized that RSB would reduce opioid consumption in patients. METHODS: Patients aged 3-14 years scheduled for laparoscopic inguinal hernia repair were randomly allocated to the RSB, local anesthetic infiltration high concentration (LAIHC), local anesthetic infiltration low concentration (LAILC), or control groups. Preoperatively, they received 0.4 ml/kg of 0.25% ropivacaine (RSB), 0.4 ml/kg of 0.25% ropivacaine (LAILC), or 0.2 ml/kg of 0.5% ropivacaine(LAIHC), and 0.2 ml/kg of normal saline (control). The primary outcome was equivalent morphine consumption. RESULTS: The authors analyzed 136 patients (RSB, 33; LAIHC, 34; LAILC, 35; control, 34). Intraoperative morphine equivalent consumption was lower in the RSB group [0.115 (0.107-0.123)] than in the LAIHC [0.144 (0.137-0.151)], LAILC [0.141 (0.134-0.149)], and control [0.160 (0.151-0.170)] groups ( P <0.001). In the post-anesthesia care unit, morphine equivalent consumption differed between the RSB [0.018 (0.010-0.027)], LAIHC [0.038 (0.028-0.049)], LAILC [0.056 (0.044-0.067)], and control [0.074 (0.063-0.084)] groups ( P <0.001). The rescue morphine equivalent consumption did not differ significantly between the RSB [0.015 (0.007-0.023)] and LAIHC [0.019 (0.010-0.029)] groups, which were lower than that in the control group [0.037 (0.029-0.045)] ( P =0.001). CONCLUSIONS: RSB can provide effective analgesia for pediatric laparoscopic inguinal hernia repair, with better effectiveness than that of LAI at the same dose.

Effect of perioperative ultrasound guided fascia iliaca compartment block in elderly adults with hip fractures undergoing arthroplasty in spinal anesthesia-a randomized controlled trial.

BACKGROUND: For elderly adults undergoing hip arthroplasty, fascia iliaca compartment block (FICB) is often used before spinal anesthesia to reduce the pain of posture placement. However, the impact of FICB within 48 h needs further study. METHODS: 89 elderly adults scheduled to undergo arthroplasty for hip fracture were enrolled and randomized into the FICB group (n = 45) and the control group (n = 44). The fascia iliaca on the operated side was located using ultrasound, and a puncture needle was placed under the fascia iliaca. The FICB group was injected with 40 ml of 0.5% ropivacaine, and the control group was injected with 40 ml of normal saline. Spinal anesthesia was performed after 20 min. Our primary outcome measures were: duration of analgesia, muscle strength, and Quality of Recovery (QoR). RESULTS: The duration of analgesia in the FICB group was 403.5 ± 39.6 min, which was longer than that (357.5 ± 35.9 min) of the control group (P = 0.012). There were 19 (42.2%) patients with muscle strength of grade 4 in the FICB group and 36 (81.8%) patients with muscle strength of grade 4 in the control group. FICB group was lower (P < 0.001). QoR-15 at 24 h after surgery was 114.1 ± 8.3 in the FICB group and 104.6 ± 8.4 in the control group (P < 0.001). QoR-15 at 48 h after surgery was 122.7 ± 8.4 in the FICB group and 120.5 ± 9.5 in the control group (P = 0.232). CONCLUSIONS: For elderly adults with hip fractures, FICB provided longer analgesia and improved 24-h QoR, but reduced postoperative muscle strength. TRAIL REGISTRATION: Chinese Clinical Registry Center, ChiCTR2200056937, 23/02/2022.

Big data mining, rational modification, and ancestral sequence reconstruction inferred multiple xylose isomerases for biorefinery.

The isomerization of xylose to xylulose is considered the most promising approach to initiate xylose bioconversion. Here, phylogeny-guided big data mining, rational modification, and ancestral sequence reconstruction strategies were implemented to explore new active xylose isomerases (XIs) for Saccharomyces cerevisiae. Significantly, 13 new active XIs for S. cerevisiae were mined or artificially created. Moreover, the importance of the amino-terminal fragment for maintaining basic XI activity was demonstrated. With the mined XIs, four efficient xylose-utilizing S. cerevisiae were constructed and evolved, among which the strain S. cerevisiae CRD5HS contributed to ethanol titers as high as 85.95 and 94.76 g/liter from pretreated corn stover and corn cob, respectively, without detoxifying or washing pretreated biomass. Potential genetic targets obtained from adaptive laboratory evolution were further analyzed by sequencing the high-performance strains. The combined XI mining methods described here provide practical references for mining other scarce and valuable enzymes.

Gallic Acid Improves Comorbid Chronic Pain and Depression Behaviors by Inhibiting P2X7 Receptor-Mediated Ferroptosis in the Spinal Cord of Rats.

Ferroptosis is an inflammatory programmed cell death process that is dependent on iron deposition and lipid peroxidation. The P2X7 receptor not only is involved in the pain process but also is closely related to the onset of depression. Gallic acid (3,4,5-trihydroxybenzoic acid), which is naturally found in a variety of plants, exhibits anti-inflammatory, antioxidant, and analgesic effects. This study established a rat model with the comorbidity of chronic constrictive injury (CCI) plus chronic unpredictable mild stress (CUMS) to explore the role and mechanism of gallic acid in the treatment of pain and depression comorbidity. Our experimental results showed that pain and depression-like behaviors were more obvious in the chronic constriction injury (CCI) plus chronic unpredictable mild stimulation (CUMS) group than they were in the sham operation group, and the P2X7-reactive oxygen species (ROS) signaling pathway was activated. The tissue iron concentration was increased, and mitochondrial damage was observed in the CCI plus CUMS group. These results were alleviated with gallic acid treatment. Therefore, we speculate that gallic acid inhibits the ferroptosis of the spinal microglia by regulating the P2X7-ROS signaling pathway and relieves the behavioral changes in rats with comorbid pain and depression.

Effect of Wearing N95 Mask on the Quality of Chest Compressions in Prehospital Emergency Personnel: A Cross-over Study.

OBJECTIVE: To evaluate the effect of wearing an N95 mask on the quality of chest compression and fatigue of prehospital emergency personnel during cardiopulmonary resuscitation (CPR). METHODS: Twenty-four eligible participants were recruited. Participants' age, sex, height, and weight were recorded. After completing the CPR training and examination, participants were tested twice, wearing surgical mask or an N95 mask, while performing chest compressions for 2 minutes. The quality of chest compression (including compression frequency, depth, rebound, and position) was recorded by the simulator. Borg fatigue scores and physiological parameters (including heart rate, mean arterial pressure, pulse oxygen saturation, and respiratory rate) were recorded before and after chest compressions. RESULTS: Compared to wearing surgical masks, participants wearing N95 masks had significantly lower quality of chest compression, including compression frequency (98.3 ± 4.9 bpm vs 104.0 ± 6.0 bpm, P < 0.001), depth (47.1 ± 4.5 mm vs 50.5 ± 5.4 mm, P < 0.001), and rebound (90.2 ± 2.7% vs 94.3 ± 2.1%, P < 0.001). The compression position was not affected. The period data showed that the difference in compression quality started after 1 minute of compressions. Participants wearing N95 masks had higher Borg fatigue scores [6.1(2) vs 5.1(2), P < 0.001], heart rates (121.2 ± 5.7 bpm vs 109.9 ± 6.0 bpm, P < 0.001), mean arterial pressures (106.3 ± 8.0 mmHg vs 99.0 ± 8.5 mmHg, P = 0.012), and respiratory rates (29.5 ± 2.7 bpm vs 24.7 ± 2.5 bpm, P < 0.001). CONCLUSION: This study showed that the use of an N95 mask by prehospital emergency personnel during the performance of chest compressions resulted in a reduction of compression quality and increased clinician fatigue. There is a need for CPR training for medical personnel wearing personal protective equipment.

Neohesperidin Alleviates the Neuropathic Pain Behavior of Rats by Downregulating the P2X4 Receptor.

Neuropathic pain (NP) is a type of chronic pain affecting 6-8% of human health as no effective drug exists. The purinergic 2X4 receptor (P2X4R) is involved in NP. Neohesperidin (NH) is a dihydroflavonoside compound, which has anti-inflammatory and antioxidative properties. This study aimed to investigate whether NH has an effect on P2X4R-mediated NP induced by chronic constriction injury (CCI) of the sciatic nerve in rats. In this study, the CCI rat model was established to observe the changes of pain behaviors, P2X4R, and satellite glial cells (SGCs) activation in dorsal root ganglion (DRG) after NH treatment by using RT-PCR, immunofluorescence double labeling and Western blotting. Our results showed CCI rats had mechanical and thermal hyperalgesia with an increased level of P2X4R. Furthermore, SGCs were activated as indicated by increased expression of glial fibrillary acidic protein and increased tumor necrosis factor-alpha receptor 1and interleukin-1ß. In addition, phosphorylated extracellular regulated protein kinases and interferon regulatory factor 5 in CCI rats increased. After NH treatment in CCI rats, the levels of above protein decreased, and the pain reduced. Overall, NH can markedly alleviate NP by reducing P2X4R expression and SGCs activation in DRG.

Comparison of LPS and MS-induced depressive mouse model: behavior, inflammation and biochemical changes.

Depression is a mental disease involving complex pathophysiological mechanisms, and there are many ways to establish depressive mouse models. The purpose of this study is to comprehensively compare the behavioral changes and its mechanism induced by two different models. This study established two depressive mouse models by maternal separation (MS) or lipopolysaccharide (LPS) administration, and added fluoxetine treatment group respectively for comparison. MS induced more apparent anxiety-like behavior while LPS induced more apparent depressive-like behavior. LPS increased peripheral inflammatory factors more apparent, which were mitigated by fluoxetine. MS inhibited the 5-HT system more obviously and was relieved by fluoxetine. LPS triggered stronger immune response in the hippocampus and prefrontal cortex (PFC). MS significantly reduced the expression of neurotrophic proteins and was alleviated by fluoxetine. Overall, LPS induced stronger system inflammation, while MS impaired the function of HPA axis and 5-HT system. Our results will contribute to a deeper understanding of the pathophysiology of different stress-induced depression and will also help researchers select appropriate models of depression for their own needs.

Pinocembrin Inhibits P2X4 Receptor-Mediated Pyroptosis in Hippocampus to Alleviate the Behaviours of Chronic Pain and Depression Comorbidity in Rats.

Neuroinflammation is critical to the comorbidity of chronic pain and depression. Pyroptosis is an inflammatory cell death that is different from apoptosis. Activation of the P2X4 receptor leads to inflammation and is involved in chronic pain and depression. Pinocembrin (5,7-dihydroxyflavanone) is a natural flavonoid compound with anti-inflammatory, antioxidant and neuroprotective effects. In this study, an animal model of chronic pain and depression comorbidity was used to explore the therapeutic effect of pinocembrin in P2X4-mediated pyroptosis. The results showed that nociceptive behaviours and depression-like behaviours were obvious in the model rats induced by chronic constrictive injury (CCI) and chronic unpredictable mild stimulus (CUMS). In the model rats, the mRNA and protein levels of the P2X4 receptor in the hippocampus were increased, and the coexpression of P2X4 and the astrocyte marker glial fibrillary acidic protein (GFAP) in the hippocampus was increased. The protein content of connexion 43 (Cx43), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 was increased. The serum content of IL-1ß and the mRNA and protein expression of IL-1ß were increased. The protein content of p-P38MAPK was increased. After treatment with pinocembrin in the model rats, these behavioural changes were improved, and the mRNA and protein levels of the above indicators were decreased. The results of molecular docking confirmed that the affinity of pinocembrin and the P2X4 receptor was - 7.8 (kcal/mol). At the same time, pinocembrin inhibited the ATP release and Ca2+ signal release in primary astrocytes and ATP-activated current of HEK293 cells transfected with the pcDNA3.0-EGFP-hP2X4 plasmid. Therefore, pinocembrin relieved nociceptive and depression-like behaviours in rats with chronic pain and depression comorbidity by inhibiting P2X4 receptor-mediated pyroptosis in the hippocampus. The mechanism of pinocembrin in treating rats with chronic pain and depression comorbidity. GJ stands for gap junction, and Cx43 is mainly expressed in astrocytes.

Beneficial Effects of lncRNA-UC.360+ shRNA on Diabetic Cardiac Sympathetic Damage via NLRP3 Inflammasome-Induced Pyroptosis in Stellate Ganglion.

Hyperglycemia is one of the common symptoms of diabetes, and it produces excessive reactive oxygen species (ROS). This study investigated whether the long noncoding RNA (lncRNA) UC.360+ is involved in diabetic cardiac autonomic neuropathy (DCAN) mediated by NLRP3 inflammasome-induced pyroptosis in the stellate ganglion (SG). Using a rat type 2 diabetes model, we found that lncRNA UC.360+ short hairpin RNA (shRNA) ameliorated the dyslipidaemia of type 2 diabetic rats and reduced serum adrenaline and ROS production in SG under hyperglycemia. In addition, UC.360+ shRNA also reduced the expression of nuclear factor kappa-B (NF-κB), NLRP3, ASC, caspase-1, interleukin-1ß (IL-1ß), and IL-18 in the SG of diabetic rats and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). Therefore, lncRNA-UC.360+ shRNA may modulate the NLRP3 inflammasome/inflammatory pathway in the SG, which in turn alleviates diabetic heart sympathetic nerve damage.

Generating Daily Soil Moisture at 16 m Spatial Resolution Using a Spatiotemporal Fusion Model and Modified Perpendicular Drought Index.

Soil moisture (SM) is an important parameter in land surface processes and the global water cycle. Remote sensing technologies are widely used to produce global-scale SM products (e.g., European Space Agency's Climate Change Initiative (ESA CCI)). However, the current spatial resolutions of such products are low (e.g., >3 km). In recent years, using auxiliary data to downscale the spatial resolutions of SM products has been a hot research topic in the remote sensing research area. A new method, which spatially downscalesan SM product to generate a daily SM dataset at a 16 m spatial resolution based on a spatiotemporal fusion model (STFM) and modified perpendicular drought index (MPDI), was proposed in this paper. (1) First, a daily surface reflectance dataset with a 16 m spatial resolution was produced based on an STFM. (2) Then, a spatial scale conversion factor (SSCF) dataset was obtained by an MPDI dataset, which was calculated based on the dataset fused in the first step. (3) Third, a downscaled daily SM product with a 16 m spatial resolution was generated by combining the SSCF dataset and the original SM product. Five cities in southern Hebei Province were selected as study areas. Two 16 m GF6 images and nine 500 m MOD09GA images were used as auxiliary data to downscale a timeseries 25 km CCI SM dataset for nine dates from May to June 2019. A total of 151 in situ SM observations collected on 1 May, 21 May, 1 June, and 11 June were used for verification. The results indicated that the downscaled SM data with a 16 m spatial resolution had higher correlation coefficients and lower RMSE values compared with the original CCI SM data. The correlation coefficients between the downscaled SM data and in situ data ranged from 0.45 to 0.67 versus 0.33 to 0.54 for the original CCI SM data; the RMSE values ranged from 0.023 to 0.031 cm3/cm3 versus 0.027 to 0.032 cm3/cm3 for the original CCI SM data. The findings described in this paper can ensure effective farmland management and other practical production applications.

A novel fermentation strategy for efficient xylose utilization and microbial lipid production in lignocellulosic hydrolysate.

The sugar utilization efficiency and the tolerance of microorganism to inhibitors are essential for lipid production from lignocellulosic biomass. In this study, the sugar consumption and inhibitor tolerance characteristics of Trichosporon dermatis 32,903 were investigated. The results showed that the lipid yield on xylose was much lower than that on glucose, while these substrates exhibited comparative efficiency for cell growth. High inoculum size improved the tolerance of T. dermatis 32,903 to inhibitors. Based on these characteristics, sugar-targeted-utilization and cyclic fermentation strategy was developed. The tolerance of high inoculum size to inhibitors was utilized, glucose was targeted for lipid fermentation and xylose was targeted for cell growth. As a result, the lipid production efficiency was greatly enhanced. The lipid titer in hydrolysate of DLCA (Densifying Lignocellulosic biomass with Chemicals followed by Autoclave) pretreated rice straw was improved to as high as 38.4 g/L with lipid yield of 0.207 g/g consumed sugar.

Transcutaneous Electrical Acupoint Stimulation Improved Preoperative Blood Pressure in Gynecological Malignant Tumor Patients With Hypertension: A Randomized, Controlled Trial.

Objective: Gynecological malignant tumor patients with hypertension, even if blood pressure is well controlled, are prone to hypertension before surgery. We plan to verify the effect of transcutaneous electrical acupoint stimulation (TEAS) on stabilizing blood pressure before operation. Methods: We enrolled 91 patients and randomly divided them into TEAS group (n=46) and control group (n=45). Patients in TEAS group received TEAS at acupoints Hegu and Neiguan. Patients in control group received transcutaneous electrical stimulation at the nonacupoint position of the upper limbs. After entering the operating room, the blood pressure before and after induction was measured. The main results were the occurrence of preinduction hypertension and postinduction hypotension. Results: There was no difference in the general information of the two groups. There were four cases (9%) of preinduction hypertension in TEAS group and 13 cases (29%) in control group. The incidence in TEAS group was significantly lower (P=0.013). There were five cases (11%) of postinduction hypotension in TEAS group and eight cases (18%) in control group. There was no significant difference between the two groups (P=0.346). The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) of the highest blood pressure before induction in TEAS group were lower than those in control group (P=0.002, 0.002, and 0.001). There was no difference in SBP, DBP, or MBP between the two groups on the day before the operation. There was no difference in the lowest blood pressure before operation between the two groups after induction. Conclusion: TEAS can prevent preinduction hypertension in patients with gynecological malignant tumors. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=143276, identifier ChiCTR2100054336.