Focused ultrasound excites action potentials in mammalian peripheral neurons in part through the mechanically gated ion channel PIEZO2.

Neurons of the peripheral nervous system (PNS) are tasked with diverse roles, from encoding touch, pain, and itch to interoceptive control of inflammation and organ physiology. Thus, technologies that allow precise control of peripheral nerve activity have the potential to regulate a wide range of biological processes. Noninvasive modulation of neuronal activity is an important translational application of focused ultrasound (FUS). Recent studies have identified effective strategies to modulate brain circuits; however, reliable parameters to control the activity of the PNS are lacking. To develop robust noninvasive technologies for peripheral nerve modulation, we employed targeted FUS stimulation and electrophysiology in mouse ex vivo skin-saphenous nerve preparations to record the activity of individual mechanosensory neurons. Parameter space exploration showed that stimulating neuronal receptive fields with high-intensity, millisecond FUS pulses reliably and repeatedly evoked one-to-one action potentials in all peripheral neurons recorded. Interestingly, when neurons were classified based on neurophysiological properties, we identified a discrete range of FUS parameters capable of exciting all neuronal classes, including myelinated A fibers and unmyelinated C fibers. Peripheral neurons were excited by FUS stimulation targeted to either cutaneous receptive fields or peripheral nerves, a key finding that increases the therapeutic range of FUS-based peripheral neuromodulation. FUS elicited action potentials with millisecond latencies compared with electrical stimulation, suggesting ion channel­mediated mechanisms. Indeed, FUS thresholds were elevated in neurons lacking the mechanically gated channel PIEZO2. Together, these results demonstrate that transcutaneous FUS drives peripheral nerve activity by engaging intrinsic mechanotransduction mechanisms in neurons [B. U. Hoffman, PhD thesis, (2019)].

Targeted ubiquitination of sensory neuron calcium channels reduces the development of neuropathic pain.

Neuropathic pain caused by lesions to somatosensory neurons due to injury or disease is a widespread public health problem that is inadequately managed by small-molecule therapeutics due to incomplete pain relief and devastating side effects. Genetically encoded molecules capable of interrupting nociception have the potential to confer long-lasting analgesia with minimal off-target effects. Here, we utilize a targeted ubiquitination approach to achieve a unique posttranslational functional knockdown of high-voltage-activated calcium channels (HVACCs) that are obligatory for neurotransmission in dorsal root ganglion (DRG) neurons. CaV-aßlator comprises a nanobody targeted to CaV channel cytosolic auxiliary ß subunits fused to the catalytic HECT domain of the Nedd4-2 E3 ubiquitin ligase. Subcutaneous injection of adeno-associated virus serotype 9 encoding CaV-aßlator in the hind paw of mice resulted in the expression of the protein in a subset of DRG neurons that displayed a concomitant ablation of CaV currents and also led to an increase in the frequency of spontaneous inhibitory postsynaptic currents in the dorsal horn of the spinal cord. Mice subjected to spare nerve injury displayed a characteristic long-lasting mechanical, thermal, and cold hyperalgesia underlain by a dramatic increase in coordinated phasic firing of DRG neurons as reported by in vivo Ca2+ spike recordings. CaV-aßlator significantly dampened the integrated Ca2+ spike activity and the hyperalgesia in response to nerve injury. The results advance the principle of targeting HVACCs as a gene therapy for neuropathic pain and demonstrate the therapeutic potential of posttranslational functional knockdown of ion channels achieved by exploiting the ubiquitin-proteasome system.

IGFBP2 induces podocyte apoptosis promoted by mitochondrial damage via integrin α5/FAK in diabetic kidney disease.

Podocyte apoptosis or loss is the pivotal pathological characteristic of diabetic kidney disease (DKD). Insulin-like growth factor-binding protein 2 (IGFBP2) have a proinflammatory and proapoptotic effect on diseases. Previous studies have shown that serum IGFBP2 level significantly increased in DKD patients, but the precise mechanisms remain unclear. Here, we found that IGFBP2 levels obviously increased under a diabetic state and high glucose stimuli. Deficiency of IGFBP2 attenuated the urine protein, renal pathological injury and glomeruli hypertrophy of DKD mice induced by STZ, and knockdown or deletion of IGFBP2 alleviated podocytes apoptosis induced by high concentration of glucose or in DKD mouse. Furthermore, IGFBP2 facilitated apoptosis, which was characterized by increase in inflammation and oxidative stress, by binding with integrin α5 (ITGA5) of podocytes, and then activating the phosphorylation of focal adhesion kinase (FAK)-mediated mitochondrial injury, including membrane potential decreasing, ROS production increasing. Moreover, ITGA5 knockdown or FAK inhibition attenuated the podocyte apoptosis caused by high glucose or IGFBP2 overexpression. Taken together, these findings unveiled the insight mechanism that IGFBP2 increased podocyte apoptosis by mitochondrial injury via ITGA5/FAK phosphorylation pathway in DKD progression, and provided the potential therapeutic strategies for diabetic kidney disease.

Platelet-rich plasma-derived exosomes enhance mesenchymal stem cell paracrine function and nerve regeneration potential.

BACKGROUND: Peripheral nerve injury (PNI) presents a significant clinical challenge, leading to enduring sensory-motor impairments. While mesenchymal stem cell (MSC)-based therapy holds promise for PNI treatment, enhancing its neurotrophic effects remains crucial. Platelet-rich plasma-derived exosomes (PRP-Exo), rich in bioactive molecules for intercellular communication, offer potential for modulating cellular biological activity. METHODS: PRP-Exo was isolated, and its impact on MSC viability was evaluated. The effects of PRP-Exo-treated MSCs (MSCPExo) on Schwann cells (SCs) from injured sciatic nerves and human umbilical vein endothelial cells (HUVECs) were assessed. Furthermore, the conditioned medium from MSCPExo (MSCPExo-CM) was analyzed using a cytokine array and validated through ELISA and Western blot. RESULTS: PRP-Exo enhanced MSC viability. Coculturing MSCPExo with SCs ameliorated apoptosis and promoted SC proliferation following PNI. Similarly, MSCPExo-CM exhibited pro-proliferative, migratory, and angiogenic effects. Cytokine array analysis identified 440 proteins in the MSCPExo secretome, with 155 showing upregulation and 6 showing downregulation, many demonstrating potent pro-regenerative properties. ELISA confirmed the enrichment of several angiotrophic and neurotrophic factors. Additionally, Western blot analysis revealed the activation of the PI3K/Akt signaling pathway in MSCPExo. CONCLUSION: Preconditioning MSCs with PRP-Exo enhanced the paracrine function, particularly augmenting neurotrophic and pro-angiogenic secretions, demonstrating an improved potential for neural repair.

Mediating Role of Rumination in Second Victim Experience to Turnover Intention in Psychiatric Nurses.

BACKGROUND: Psychiatric nurses often face patient safety incidents that can cause physical and emotional harm, even leading to s econd victim syndrome and staff shortages. Rumination-a common response after nurses suffer a patient safety event-may play a specific role between the second victim experience and turnover intention. Understanding these mechanisms is crucial for supporting psychiatric nurses and retaining psychiatric nursing resources. OBJECTIVES: The study aimed to explore the associations among second victim experience, rumination, and turnover intention in psychiatric nurses and confirm how second victim experience influences turnover intention through rumination and its subtypes. METHODS: A descriptive, cross-sectional study was adapted to survey 252 psychiatric nurses who experienced a patient safety incident at three hospitals in China between March and April 2023. We used the Sociodemographic and Patient Safety Incident Characteristics Questionnaire (the Chinese version of the Second Victim Experience and Support Tool), the Event-Related Rumination Inventory, and the Turnover Intention Scale. Path analysis with bootstrapping was employed to accurately analyze and estimate relationships among the study variables. RESULTS: There was a positive association between second victim experience and turnover intention. In addition, both invasive and deliberate rumination showed significant associations with second victim experience and turnover intention. Notably, our results revealed that invasive and deliberate rumination played partial mediating roles in the relationship between second victim experience and turnover intention in psychiatric nurses. DISCUSSION: The negative experience and turnover intention of the psychiatric nurse second victims are at a high level. Our results showed that invasive rumination positively mediated the relationship between second victim experience and turnover intention, and deliberate rumination could weaken this effect. This study expands the knowledge of the mechanisms underlying the effect of the second victim experience on turnover intention. Organizations must attach importance to the professional dilemmas of the psychiatric nurses' second victims. Nurse managers can reduce nurses' turnover intention by taking measures to reduce invasive rumination and fostering deliberate meditation to help second victims recover from negative experiences.

Evaluation of bladder filling effects on the dose distribution during radiotherapy for cervical cancer based on daily CT images.

PURPOSE: This study aimed to assess the effects of bladder filling during cervical cancer radiotherapy on target volume and organs at risk (OARs) dose based on daily computed tomography (daily-CT) images and provide bladder-volume-based dose prediction models. METHODS: Nineteen patients (475 daily-CTs) comprised the study group, and five patients comprised the validation set (25 daily-CTs). Target volumes and OARs were delineated on daily-CT images and the treatment plan was recalculated accordingly. The deviation from the planning bladder volume (DVB), the correlation between DVB and clinical (CTV)/planning (PTV) target volume in terms of prescribed dose coverage, and the relationship of small bowel volume and bladder dose with the ratio of bladder volume (RVB) were analyzed. RESULTS: In all cases, the prescribed dose coverage in the CTV was >95% when DVB was <200 cm3 , whereas that in the PTV was >95% when RVB was <160%. The ratio of bladder V45 Gy to the planning bladder V45 Gy (RBV45 ) exhibited a negative linear relationship with RVB (RBV45  = -0.18*RVB + 120.8; R2  = 0.80). Moreover, the ratio of small bowel volume to planning small bowel volume (RVS) exhibited a negative linear relationship with RVB (RVS = -1.06*RVB +217.59; R2  = 0.41). The validation set results showed that the linear model predicted well the effects of bladder volume changes on target volume coverage and bladder dose. CONCLUSIONS: This study assessed dosimetry and volume effects of bladder filling on target and OARs based on daily-CT images. We established a quantitative relationship between these parameters, providing dose prediction models for cervical cancer radiotherapy.

LncRNA-HOTAIR promotes endothelial cell pyroptosis by regulating the miR-22/NLRP3 axis in hyperuricaemia.

Long non-coding RNA (lncRNA) plays an important role in the renal inflammatory response caused by hyperuricaemia. However, the underlying molecular mechanisms through which lncRNA is involved in endothelial injury induced by hyperuricaemia remain unclear. In this study, we investigated the regulatory role of lncRNA-HOTAIR in high concentration of uric acid (HUA)-induced renal injury. We established hyperuricaemia mouse model and an in vitro uric acid (UA)-induced human umbilical vein endothelial cell (HUVEC) injury model. In HUA-treated HUVECs and hyperuricaemia mice, we observed increased HOTAIR and decreased miR-22 expression. The expression of pyroptosis-associated protein (NLRP3, Caspase-1, GSDMD-N, GSDMD-FL) was increased. The release of LDH, IL-1ß and IL-18 in cell supernatants and the sera of model mice was also increased. The proliferation of HUVECs stimulated by HUA was significantly inhibited, and the number of TUNEL-positive cells in hyperuricaemia mouse kidney was increased. Bioinformatics analysis and luciferase reporter and RIP assays confirmed that HOTAIR promoted NLRP3 inflammasome activation by competitively binding miR-22. In gain- or loss-of-function experiments, we found that HOTAIR and NLRP3 overexpression or miR-22 knock down activated the NLRP3 inflammasome and promoted pyroptosis in HUA-treated HUVECs, while NLRP3 and HOTAIR knockdown or a miR-22 mimic exerted the opposite effects. Furthermore, in vivo experiments validated that HOTAIR knockdown alleviated renal inflammation in hyperuricaemia mice. In conclusion, we demonstrated that in hyperuricaemia, lncRNA-HOTAIR promotes endothelial cell pyroptosis by competitively binding miR-22 to regulate NLRP3 expression.

Development and validation of a model for the early prediction of the RRT requirement in patients with rhabdomyolysis.

INTRODUCTION: Rhabdomyolysis (RM) is a complex set of clinical syndromes involving the rapid dissolution of skeletal muscles. The early detection of patients who need renal replacement therapy (RRT) is very important and may aid in delivering proper care and optimizing the use of limited resources. METHODS: Retrospective analyses of the following three databases were performed: the eICU Collaborative Research Database (eICU-CRD), the Medical Information Mart for Intensive Care III (MIMIC-III) database and electronic medical records from the First Medical Centre of the Chinese People's Liberation Army General Hospital (PLAGH). The data from the eICU-CRD and MIMIC-III datasets were merged to form the derivation cohort. The data collected from the Chinese PLAGH were used for external validation. The factors predictive of the need for RRT were selected using a LASSO regression analysis. A logistic regression was selected as the algorithm. The model was built in Python using the ML library scikit-learn. The accuracy of the model was measured by the area under the receiver operating characteristic curve (AUC). R software was used for the LASSO regression analysis, nomogram, concordance index, calibration, and decision and clinical impact curves. RESULTS: In total, 1259 patients with RM (614 patients from eICU-CRD, 324 patients from the MIMIC-III database and 321 patients from the Chinese PLAGH) were eligible for this analysis. The rate of RRT was 15.0% (92/614) in the eICU-CRD database, 17.6% (57/324) in the MIMIC-III database and 5.6% in the Chinese PLAGH (18/321). After the LASSO regression selection, eight variables were included in the RRT prediction model. The AUC of the model in the training dataset was 0.818 (95% CI 0.78-0.87), the AUC in the test dataset was 0.794 (95% CI 0.72-0.86), and the AUC in the Chinese PLAGH dataset (external validation dataset) was 0.820 (95% CI 0.70-0.86). CONCLUSIONS: We developed and validated a model for the early prediction of the RRT requirement among patients with RM based on 8 variables commonly measured during the first 24 h after admission. Predicting the need for RRT could help ensure appropriate treatment and facilitate the optimization of the use of medical resources.

The top 100 most cited articles on rhabdomyolysis: A bibliometric analysis.

INTRODUCTION: Over the past few decades, the incidence of Rhabdomyolysis (RM) has significantly increased. The prognosis is substantially worse if renal failure develops. Many problems remain to be addressed regarding the pathogenesis, prevention, and treatment of RM. The purpose of this study was to identify and characterize the top 100 most cited publications regarding rhabdomyolysis (RM) by performing a bibliometric analysis. METHODS: Publications focusing on RM were identified from the Science Citation Index-Expanded (SCI-E) of the Web of Science Core Collection (WoSCC). Bibliographic information was collected, including year of publication, authorship, publishing journals, institution, country of origin and keywords. CiteSpace V5.6.R2 and the Online Analysis Platform of Literature Metrology were used for descriptive analysis. RESULTS: The 100 most cited articles were published between 1995 and 2016, with citation numbers ranging from 116 to 904. The United States (60) has been the largest contributor to RM research. Hartford Hospital and University of Texas were found to be the most productive institutions, with five articles each. Thompson, PD, who authored six articles, was the most productive author. The American Journal of Cardiology published the most articles (5), followed by the New England Journal of Medicine (4). The top three co-cited journals were the New England Journal of Medicine (74), Lancet (59) and JAMA (54). CONCLUSIONS: This study provides valuable information on the study of RM. These findings may be used to guide clinical decision-making and identify new research fields.

Research Progress on the Role of Inflammasomes in Kidney Disease.

Inflammasomes are multimeric complexes composed of cytoplasmic sensors, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC or PYCARD), and procaspase-1 and play roles in regulating caspase-dependent inflammation and cell death. Inflammasomes are assembled by sensing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) and initiate inflammatory responses by activating caspase-1. Activated caspase-1 promotes the release of the inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 and eventually induces pyroptosis. Inflammasomes are closely related to kidney diseases. In particular, the NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome has been shown to cause acute and chronic kidney diseases by regulating canonical and noncanonical mechanisms of inflammation. Small-molecule inhibitors that target NLRP3 and other components of the inflammasome are potential options for the treatment of kidney-related diseases such as diabetic nephropathy. This article will focus on the research progress on inflammasomes and the key pathogenic roles of inflammasomes in the development and progression of kidney diseases and explore the potential of this intracellular inflammation to further prevent or block the development of the kidney disease.

Extracorporeal shockwave therapy for the treatment of knee osteoarthritis: a meta-analysis.

PURPOSE: Extracorporeal shockwave therapy (ESWT) has become a common practice for treating knee osteoarthritis (OA). However, the effectiveness and safety of this treatment are still questionable. This meta-analysis is aimed at determining the degree of pain reduction and functional outcome after ESWT for knee OA. METHODS: We systematically searched MEDLINE, EMBASE, and other online databases. The articles comparing the outcomes between ESWT and controls were included in the analysis. RESULTS: Nine studies with 705 patients were included. The pooled data revealed significantly lower pain scores in the ESWT groups than in the control groups within two weeks of treatment and six months after treatment (visual analogue scale, - 1.59, p = 0.0003, 95% confidence interval (CI) - 2.45 to - 0.72 at 2 weeks; - 1.12, p = 0.005, 95% CI - 1.89 to - 0.34 at 6 months). The ESWT group also had better functional outcomes four to six weeks post treatment (Western Ontario and McMaster Universities Osteoarthritis Index, - 11.96, p = 0.003, 95% CI - 19.76 to - 4.15). No rebound pain was noted for up to 12 months. CONCLUSION: Using ESWT to treat knee OA may reduce pain and improve functional outcomes. The effect may last six months to one year. More prospective studies are needed to investigate the settings for ESWT to optimize treatment results.

Inhibition Mediated by Glycinergic and GABAergic Receptors on Excitatory Neurons in Mouse Superficial Dorsal Horn Is Location-Specific but Modified by Inflammation.

The superficial dorsal horn is the synaptic termination site for many peripheral sensory fibers of the somatosensory system. A wide range of sensory modalities are represented by these fibers, including pain, itch, and temperature. Because the involvement of local inhibition in the dorsal horn, specifically that mediated by the inhibitory amino acids GABA and glycine, is so important in signal processing, we investigated regional inhibitory control of excitatory interneurons under control conditions and peripheral inflammation-induced mechanical allodynia. We found that excitatory interneurons and projection neurons in lamina I and IIo are dominantly inhibited by GABA while those in lamina IIi and III are dominantly inhibited by glycine. This was true of identified neuronal subpopulations: neurokinin 1 receptor-expressing (NK1R+) neurons in lamina I were GABA-dominant while protein kinase C gamma-expressing (PKCγ+) neurons at the lamina IIi-III border were glycine-dominant. We found this pattern of synaptic inhibition to be consistent with the distribution of GABAergic and glycinergic neurons identified by immunohistochemistry. Following complete Freund's adjuvant injection into mouse hindpaw, the frequency of spontaneous excitatory synaptic activity increased and inhibitory synaptic activity decreased. Surprisingly, these changes were accompanied by an increase in GABA dominance in lamina IIi. Because this shift in inhibitory dominance was not accompanied by a change in the number of inhibitory synapses or the overall postsynaptic expression of glycine receptor α1 subunits, we propose that the dominance shift is due to glycine receptor modulation and the depressed function of glycine receptors is partially compensated by GABAergic inhibition.SIGNIFICANCE STATEMENT Pain associated with inflammation is a sensation we would all like to minimize. Persistent inflammation leads to cellular and molecular changes in the spinal cord dorsal horn, including diminished inhibition, which may be responsible for enhance excitability. Investigating inhibition in the dorsal horn following peripheral inflammation is essential for development of improved ways to control the associated pain. In this study, we have elucidated regional differences in inhibition of excitatory interneurons in mouse dorsal horn. We have also discovered that the dominating inhibitory neurotransmission within specific regions of dorsal horn switches following peripheral inflammation and the accompanying hypersensitivity to thermal and mechanical stimuli. Our novel findings contribute to a more complete understanding of inflammatory pain.

Oxidized Low-Density Lipoprotein-Deteriorated Psoriasis Is Associated with the Upregulation of Lox-1 Receptor and Il-23 Expression In Vivo and In Vitro.

Psoriasis is a chronic inflammatory skin disease. Even though scientists predict that abnormalities in lipid metabolism play an important role in the pathogenesis of psoriasis, the actual underlying mechanisms are still unclear. Therefore, understanding the possible relationship between mechanisms of the occurrence of psoriasis and dyslipidemia is an important issue that may lead to the development of effective therapies. Under this principle, we investigated the influences of hyperlipidemia in imiquimod (IMQ)-induced psoriasis-like B6.129S2-Apoetm1Unc/J mice and oxidized low-density lipoprotein (oxLDL) in tumor necrosis factor (TNF)-α-stimulated Hacat cells. In our study, we showed that a high-cholesterol diet aggravated psoriasis-like phenomena in IMQ-treated B6.129S2-Apoetm1Unc/J mice. In vitro analysis showed that oxLDL increased keratinocyte migration and lectin-type oxLDL receptor 1 (LOX-1) expression. Evidence suggested that interleukin (IL)-23 was a main cytokine in the pathogenesis of psoriasis. High-cholesterol diet aggravated IL-23 expression in IMQ-treated B6.129S2-Apoetm1Unc/J mice, and oxLDL induced IL-23 expression mediated by LOX-1 in TNF-α-stimulated Hacat cells. Therefore, it will be interesting to investigate the factors for the oxLDL induction of LOX-1 in psoriasis. LOX-1 receptor expression may be another novel treatment option for psoriasis and might represent the most promising strategy.

[Chemotaxis response of Erwinia carotovora on sugars and amino acids of root exudates of Panax ginseng].

The chemotaxis response of Erwinia carotovora to different sugars and amino acids in four kinds of chemotactic parameters (concentration, time, temperature and pH ) was determined by capillary method. The results showed that when pH was 8, concentration was 0.025 mg•L ⁻¹, culture temperature was 25 ℃ and the duration was 60 minutes, the optimal chemotaxis rate of lysine was 2.509,when pH was 6, concentration was 0.25 mg•L ⁻¹, culture temperature was 25 ℃ and the duration was 60 minutes, the optimal chemotaxis rate of arginine was 2.218 8,when pH was 7, concentration was 0.25 mg•L ⁻¹, culture temperature was 30 ℃ and the duration was 60 minutes, the optimal chemotaxis rate of L-rhamnose was 3.091 2, when pH was 6, concentration was 0.25 mg•L ⁻¹, culture temperature was 30 ℃ and the duration was 45 minutes, the optimal chemotaxis rate of D-arabinose was 3.026 3. Sugars and amino acids had obvious chemotaxis with E. carotovora,the high concentration of carbohydrate and amino acid exited an inhibitory effect on chemotaxis response of E. carotovora, and the chemotaxis response decreased with the increase of concentration of carbohydrates and amino acids.

Synaptic GluN2A and GluN2B containing NMDA receptors within the superficial dorsal horn activated following primary afferent stimulation.

NMDA receptors are important elements in pain signaling in the spinal cord dorsal horn. They are heterotetramers, typically composed of two GluN1 and two of four GluN2 subunits: GluN2A-2D. Mice lacking some of the GluN2 subunits show deficits in pain transmission yet functional synaptic localization of these receptor subtypes in the dorsal horn has not been fully resolved. In this study, we have investigated the composition of synaptic NMDA receptors expressed in monosynaptic and polysynaptic pathways from peripheral sensory fibers to lamina I neurons in rats. We focused on substance P receptor-expressing (NK1R+) projection neurons, critical for expression of hyperalgesia and allodynia. EAB-318 and (R)-CPP, GluN2A/B antagonists, blocked both monosynaptic and polysynaptic NMDA EPSCs initiated by primary afferent activation by ∼90%. Physiological measurements exploiting the voltage dependence of monosynaptic EPSCs similarly indicated dominant expression of GluN2A/B types of synaptic NMDA receptors. In addition, at synapses between C fibers and NK1R+ neurons, NMDA receptor activation initiated a secondary, depolarizing current. Ifenprodil, a GluN2B antagonist, caused modest suppression of monosynaptic NMDA EPSC amplitudes, but had a widely variable, sometimes powerful, effect on polysynaptic responses following primary afferent stimulation when inhibitory inputs were blocked to mimic neuropathic pain. We conclude that GluN2B subunits are moderately expressed at primary afferent synapses on lamina I NK1R+ neurons, but play more important roles for polysynaptic NMDA EPSCs driven by primary afferents following disinhibition, supporting the view that the analgesic effect of the GluN2B antagonist on neuropathic pain is at least in part, within the spinal cord.

[Research of chemotaxis response of Botrytis cinerea and Alternaria panax on total ginsenosides].

In this paper, three kinds of chemotactic parameters (concentration, temperature and pH) were determined by plate assay and spore germination method to research the chemotactic response of Botrytis cinerea and Alternaria panax, and their spores on total ginsenosides. The results showed that Botrytis cinerea had strong chemotactic response at the mid-concentration of total ginsenosides (cultivation temperature was 20 degrees C and pH value was 6), and the data of chemotactic migration index (CMI) was 1.293 0, chemotactic growth rate (CGR) was 0.476 0, spore germination rate (SGR) was 53%, and dry weight of mycelial (DWM) was 0.452 6 g x L(-1); however, Alternaria panax had strong chemotactic response at the low-concentration of total ginsenosides (cultivation temperature was 25 degrees C and pH value was 6), and the data of chemotactic migration index (CMI) was 1.235 4, chemotactic growth rate (CGR) was 0.537 0, spore germination rate (SGR) was 67%, and dry weight of mycelial (DWM) was 0.494 8 g x L(-1). The results indicated that the low and middle concentration (2, 20 mg x L(-1)) of total ginsenosides had significant promoting effect on chemotactic response of these two pathogens, and the spore germination, mycelial growth rate, dry weight of mycelial of them were also significantly improved by this chemotactic response, whereas it decreased as the increase of total ginsenosides concentration.

Knowledge mapping of UMOD of English published work from 1985 to 2022: a bibliometric analysis.

BACKGROUND: UMOD is exclusively produced by renal epithelial cells. Recent genome-wide association studies (GWAS) suggested that common variants in UMOD gene are closely connected with the risk of CKD. However, a comprehensive and objective report on the current status of UMOD research is lacking. Therefore, we aim to conduct a bibliometric analysis to quantify and identify the status quo and trending issues of UMOD research in the past. METHODS: We collected data from the Web of Science Core Collection database and used the Online Analysis Platform of Literature Metrology, the Online Analysis Platform of Literature Metrology and Microsoft Excel 2019 to perform bibliometricanalysis and visualization. RESULTS: Based on the data from the WoSCC database from 1985 to 2022, a total of 353 UMOD articles were published in 193 academic journals by 2346 authors from 50 different countries/regions and 396 institutions. The United States published the most papers. Professor Devuyst O from University of Zurich not only published the greatest number of UMOD-related papers but also is among the top 10 co-cited authors. KIDNEY INTERNATIONAL published the most necroptosis studies, and it was also the most cited journal. High-frequency keywords mainly included 'chronic kidney disease', 'Tamm Horsfall protein' and 'mutation'. CONCLUSIONS: The number of UMOD-related articles has steadily increased over the past decades Current UMOD studies focused on Biological relevance of the UMOD to kidney function and potential applications in the risk of CKD mechanisms, these might provide ideas for further research in the UMOD field.

Merkel cells and keratinocytes in oral mucosa are activated by mechanical stimulation.

The detection of mechanical qualities of foodstuffs is essential for nutrient acquisition, evaluation of food freshness, and bolus formation during mastication. However, the mechanisms through which mechanosensitive cells in the oral cavity transmit mechanical information from the periphery to the brain are not well defined. We hypothesized Merkel cells, which are epithelial mechanoreceptors and important for pressure and texture sensing in the skin, can be mechanically activated in the oral cavity. Using live-cell calcium imaging, we recorded Merkel cell activity in ex vivo gingival and palatal preparations from mice in response to mechanical stimulation. Merkel cells responded with distinct temporal patterns and activation thresholds in a region-specific manner, with Merkel cells in the hard palate having a higher mean activation threshold than those in the gingiva. Unexpectedly, we found that oral keratinocytes were also activated by mechanical stimulation, even in the absence of Merkel cells. This indicates that mechanical stimulation of oral mucosa independently activates at least two subpopulations of epithelial cells. Finally, we found that oral Merkel cells contribute to preference for consuming oily emulsion. To our knowledge, these data represent the first functional study of Merkel-cell physiology and its role in flavor detection in the oral cavity.

Renal inflammation combined with renal function reserve reduction accelerate kidney aging via pentose phosphate pathway.

Aging is closely associated with inflammation, which affects renal function reserve (RFR) in the kidneys. This study aims to investigate the impact of reduced RFR reduction on kidney aging and the influence of renal inflammation and RFR reduction on this process. Natural aging rats and those subjected to unilateral nephrectomy (UNX), 1/6 nephrectomy (1/6NX), and unilateral ureteral obstruction (UUO) were observed at 6, 12, 18, and 21 months. Our findings suggest that RFR reduction and renal inflammation can accelerate kidney aging, and inflammation contributes more. Metabolomics analysis revealed alterations in amino acid metabolism contribute to RFR decline. Furthermore, experiments in vitro confirmed the involvement of pentose phosphate pathway (PPP) in promoting aging though inflammation. Our research provides novel insights into for the mechanism of kidney aging and provides indirect support for clinical treatment decisions, such as addressing kidney inflammation, stones, or tumors that may necessitate partial or complete nephrectomy.

Associated Factors of Patients' Survival in Out of Hospital Cardiac Arrest; a Cross-sectional Study.

Introduction: Chinese populations have an increasingly high prevalence of cardiac arrest. This study aimed to investigate the prehospital associated factors of survival to hospital admission and discharge among out-of-hospital cardiac arrest (OHCA) adult cases in Macao Special Administrative Region (SAR), China. Methods: Baseline characteristics as well as prehospital factors of OHCA patients were collected from publicly accessible medical records and Macao Fire Services Bureau, China. Demographic and other prehospital OHCA characteristics of patients who survived to hospital admission and discharge were analyzed using multivariate logistic regression analysis. Results: A total of 904 cases with a mean age of 74.2±17.3 (range: 18-106) years were included (78%>65 years, 62% male). Initial shockable cardiac rhythm was the strongest predictor for survival to both hospital admission (OR=3.57, 95% CI: 2.26-5.63; p<0.001) and discharge (OR=12.40, 95% CI: 5.70-26.96; p<0.001). Being male (OR=1.63, 95% CI:1.08-2.46; p =0.021) and the lower emergency medical service (EMS) response time (OR=1.62, 95% CI: 1.12-2.34; p =0.010) were also associated with a 2-fold association with survival to hospital admission. In addition, access to prehospital defibrillation (OR=4.25, 95% CI: 1.78-10.12; p <0.001) had a 4-fold association with survival to hospital discharge. None of these associations substantively increased with age. Conclusion: The major OHCA predictors of survival were initial shockable cardiac rhythm, being male, lower EMS response time, and access to prehospital defibrillation. These findings indicate a need for increased public awareness and more education.