Unraveling the Contribution of MulSOS2 in Conferring Salinity Tolerance in Mulberry (Morus atropurpurea Roxb).

Salinity is one of the most serious threats to sustainable agriculture. The Salt Overly Sensitive (SOS) signaling pathway plays an important role in salinity tolerance in plants, and the SOS2 gene plays a critical role in this pathway. Mulberry not only has important economic value but also is an important ecological tree species; however, the roles of the SOS2 gene associated with salt stress have not been reported in mulberry. To gain insight into the response of mulberry to salt stress, SOS2 (designated MulSOS2) was cloned from mulberry (Morus atropurpurea Roxb), and sequence analysis of the amino acids of MulSOS2 showed that it shares some conserved domains with its homologs from other plant species. Our data showed that the MulSOS2 gene was expressed at different levels in different tissues of mulberry, and its expression was induced substantially not only by NaCl but also by ABA. In addition, MulSOS2 was exogenously expressed in Arabidopsis, and the results showed that under salt stress, transgenic MulSOS2 plants accumulated more proline and less malondialdehyde than the wild-type plants and exhibited increased tolerance to salt stress. Moreover, the MulSOS2 gene was transiently overexpressed in mulberry leaves and stably overexpressed in the hairy roots, and similar results were obtained for resistance to salt stress in transgenic mulberry plants. Taken together, the results of this study are helpful to further explore the function of the MulSOS2 gene, which provides a valuable gene for the genetic breeding of salt tolerance in mulberry.

Characterization of the complete plastome sequence of Korean endemic, Cardamine glechomifolia H.Lév. (Brassicaceae, Brassicales).

In this study, we report the complete plastome sequence of Cardamine glechomifolia H.Lév. 1913 (NCBI acc. no. OP894664). This plastome shows typical quadripartite structure. The plastome size is 154,307 bp, which consists of 84,015 bp large single-copy (LSC), 17,690 bp small single-copy (SSC), and 26,301 bp inverted repeat (IR) regions. The plastome contains 112 genes, including 78 protein-coding, 30 tRNA, and four rRNA genes. The infA gene is pseudogenized. Sixteen genes contain one intron and two genes (clpP and ycf3) have two introns. The phylogenomic analysis conducted in our study reveals that the genus Cardamine, which encompasses C. glechomifolia, exhibits three distinct clades. In order to elucidate the interrelationship among the three clades, it is imperative to conduct additional investigations by augmenting the number of Cardamine samples.

Chemical Constituents of Halophyte Suaeda glauca and Their Therapeutic Potential for Hair Loss.

Suaeda glauca, a halophyte in the Amaranthaceae family, exhibits remarkable resilience to high salt and alkali stresses despite the absence of salt glands or vesicles in its leaves. While there is growing pharmacological interest in S. glauca, research on its secondary metabolites remains limited. In this study, chemical constituents of the aerial parts of S. glauca were identified using 1D- and 2D-NMR experiments, and its biological activity concerning hair loss was newly reported. Eight compounds, including alkaloids (1~3), flavonoids (4~6), and phenolics (7 and 8), were isolated. The compounds, except the flavonoids, were isolated for the first time from S. glauca. In the HPLC chromatogram, quercetin-3-O-ß-d-glucoside, kaempferol-3-O-ß-d-glucoside, and kaempferol were identified as major constituents in the extract of S. glauca. Additionally, the therapeutic potential of the extract of S. glauca and the isolated compounds 1~8 on the expressions of VEGF and IGF-1, as well as the regulation of Wnt/ß-catenin signaling, were evaluated in human follicle dermal papilla cells (HFDPCs) and human umbilical vein endothelial cells (HUVECs). Among the eight compounds, compound 4 was the most potent in terms of increasing the expression of VEGF and IGF-1 and the regulation of Wnt/ß-catenin. These findings suggest that S. glauca extract and its compounds are potential new candidates for preventing or treating hair loss.

The efficacy of intradermal hyaluronic acid filler as a skin quality booster: A prospective, single-center, single-arm pilot study.

BACKGROUND: The use of "skin boosters" comprised of hyaluronic acid (HA)-based fillers to improve skin quality has gained popularity recently, especially in individuals interested in skin rejuvenation. AIM: This study aimed to evaluate the efficacy and safety of intradermal micropuncture injections of HA-based gel filler combined with lidocaine (BYRYZN® SKINBOOSTER HA, ACROSS Co., Ltd., Gangwon-do, Korea). PATIENTS/METHODS: A prospective, single-arm, open-label pilot study was conducted with study subjects who were aged between 30 and 60 years old and exhibited evidence of skin aging, such as wrinkles and loss of elasticity. They received three injections at 2-week intervals and were followed up for a total of 12 weeks. RESULTS: Twenty subjects with a mean age of 54.1 years were included. The mean Lemperle wrinkle scale demonstrated a 40% decrease from 2.60 ± 0.60 at baseline to 1.55 ± 0.51 at week 8. The improvement rate was maintained at about 33% until week 12. The average maximum height of the wrinkle (Rz, µm), average skin roughness (Ra, µm), skin elasticity (R2, AU), facial curved length (mm), skin pore size (mm2 ), skin hydration (AU), TEWL (g/hm2 ), and skin glossiness (gloss value, AU) exhibited statistically significant improvements over time compared with the baseline measurements. No serious adverse effects or persistent adverse effects were reported, except for a transient subcutaneous nodule in one subject. CONCLUSIONS: This study demonstrates that multiple microinjections of HA-based gel filler for facial skin aging are safe and effective in improving facial skin quality.

Effects of ulinastatin therapy in deep vein thrombosis prevention after brain tumor surgery: A single-center randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) is a common neurosurgical complication after brain tumor resection, and its prophylaxis has been widely studied. There are no effective drugs in the clinical management of venous thromboembolism, and there is an absence of evidence-based medicine concerning the treatment of severe multiple traumas. AIM: To explore whether ulinastatin (UTI) can prevent VTE after brain tumor resection. METHODS: The present research included patients who underwent brain tumor resection. Patients received UTIs (400,000 IU) or placebos utilizing computer-based random sequencing (in a 1:1 ratio). The primary outcome measures were the incidence of VTE, coagulation function, pulmonary emboli, liver function, renal function, and drug-related adverse effects. RESULTS: A total of 405 patients were evaluated between January 2019 and December 2021, and 361 of these were initially enrolled in the study to form intention-to-treat, which was given UTI (n = 180) or placebo (n = 181) treatment in a random manner. There were no statistically significant differences in baseline clinical data between the two groups. The incidence of VTE in the UTI group was remarkably improved compared with that in the placebo group. UTI can improve coagulation dysfunction, pulmonary emboli, liver function, and renal function. No significant difference was identified between the two groups in the side effects of UTI-induced diarrhea, vomiting, hospital stays, or hospitalization costs. The incidence of allergies was higher in the UTI group than in the placebo group. CONCLUSION: The findings from the present research indicated that UTI can decrease the incidence of VTE and clinical outcomes of patients after brain tumor resection and has fewer adverse reactions.

[Preparation of vitexin albumin nanoparticles and its pharmacokinetic study].

This study aims to prepare vitexin albumin nanoparticles(VT-BSA-NPs) to alleviate the low bioavailability of vitexin(VT) in vivo due to its poor water solubility. VT micro powders were prepared by the antisolvent crystallization method, and the morphology, size, and physicochemical properties of VT micro powders were studied. The results showed that the VT micro powder had a particle size of(187.13±7.15) nm, an approximate spherical morphology, and a uniform size distribution. Compared with VT, the chemical structure of VT micro powders has not changed. VT-BSA-NPs were prepared from VT micro powders by desolvation-crosslinking curing method. The preparation process was screened by single factor test and orthogonal test, and the quality evaluation of the optimal prescription particle size, PDI, Zeta potential, EE, and morphology was performed. The results showed that the average particle size of VT-BSA-NPs was(124.33±0.47) nm; the PDI was 0.184±0.012; the Zeta potential was(-48.83±2.20) mV, and the encapsulation rate was 83.43%±0.39%, all of which met the formulation-related requirements. The morphological results showed that the VT-BSA-NPs were approximately spherical in appearance, regular in shape, and without adhesion on the surface. In vitro release results showed a significantly reduced release rate of VT-BSA-NPs compared with VT, indicating a good sustained release effect. LC-MS/MS was used to establish an analytical method for in vivo analysis of VT and study the plasma pharmacokinetics of VT-BSA-NPs in rats. The results showed that the specificity of the analytical method was good, and the extraction recovery was more than 90%. Compared with VT and VT micro powders, VT-BSA-NPs could significantly increase AUC, MRT, and t_(1/2), which was beneficial to improve the bioavailability of VT.

[Multi-Detector CT Findings of Typical and Atypical Appendicitis: A Pictorial Essay]. / ì „í˜•ì  및 ë¹„ì „í˜•ì  충수염의 다중검출기컴퓨터단층촬영 소견: 임상화보.

Multi-detector CT (MDCT) is a highly accurate diagnostic tool that is commonly used to evaluate appendicitis and its complications. The diagnosis of appendicitis based on MDCT findings can be difficult and challenging when the observed findings are inconsistent with the typical features. Atypical appendicitis includes a wide spectrum of features, such as variable positions of the appendix and cecum, complications, and unusual pathological findings of secondary appendicitis that mimic or induce appendicitis. Our pictorial essay describes the diverse spectrum of atypical appendicitis and appendicitis-like conditions in terms of location abnormalities, complications, and uncommon pathologies, including related tumors, reactive appendicitis, appendiceal diverticulitis, and IgG4-related disease. Through this essay, the readers can become more familiar with MDCT findings of atypical appendicitis.

[Photosynthetic characteristics of Leymus chinensis and Medicago sativa in artificial grassland]. / ç¾Šè‰å’Œç´«èŠ±è‹œè“¿äººå·¥è‰åœ°å ‰åˆç‰¹æ€§.

To explore the effect of monoculture and mixture sowing artificial grassland on the photosynthetic characteristics of Leymus chinensis and Medicago sativa, we determined the diurnal variation of photosynthetic properties of L. chinensis and M. sativa under different treatments. The results showed that the diurnal changes of net photosynthetic rate, blade temperature and transpiration rate of L. chinensis and M. sativa showed 'unimodal type' in monoculture, the stomatal conductance of M. sativa showed 'unimodal type', and the stomatal conductance and water use efficiency of L. chinensis showed 'bimodal type'. Under the mixed sowing treatment, the diurnal changes of net photosynthetic rate, blade temperature and transpiration rate of L. chinensis and M. sativa showed 'unimodal type', the stomatal conductance and water use efficiency of L. chinensis showed 'unimodal type', and the stomatal conductance of M. sativa showed 'bimodal type'. The peak photosynthetic rate of L. chinensis under mixture was signi-ficantly higher than that under monoculture, being 17.72 and 13.65 µmol CO2·m-2·s-1, respectively. Under monoculture and mixture sowing treatments, the chlorophyll content of L. chinensis was higher than that of M. sativa, nitrogen content of the leaves of L. chinensis was lower than that of M. sativa, and the nitrogen content in the leaves of mixture sowing L. chinensis was significantly higher than that of monoculture sowing L. chinensis, which were 27.60 and 22.55 g·kg-1, respectively. Net photosynthetic rates of L. chinensis and M. sativa were significantly positively correlated with stomatal conductance and transpiration rate, and significantly negatively correlated with intercellular CO2 concentration under different planting methods. Net photosynthetic rate of M. sativa was significantly positively correlated with blade temperature and water use efficiency. In summary, mixed sowing was beneficial to enhance nitrogen content of L. chinensis. Our results provided a theoretical basis for the response of the photosynthetic characteristics of forage to planting mode of artificial grassland.

Coinfection With Severe Fever With Thrombocytopenia Syndrome and Scrub Typhus in Korea.

Background: Scrub typhus and severe fever with thrombocytopenia syndrome (SFTS) are the 2 most common tick-borne infectious diseases in Korea. Every year, an increasing number of cases are reported, which is a public health concern. Therefore, we aimed to investigate the prevalence of SFTS-scrub typhus coinfection in patients with SFTS. Methods: Clinical samples were collected from 129 patients with SFTS. One-step reverse-transcription polymerase chain reaction (PCR) was performed to identify the SFTS virus (SFTSV), and real-time PCR followed by nested PCR was performed to detect the Orientia tsutsugamushi gene for scrub typhus. Phylogenetic analysis was conducted to confirm the evolutionary relationships among different species. Results: Among 129 SFTS cases, 2 patients with SFTSV were positive for O. tsutsugamushi with a prevalence of coinfection of 1.6% (95% confidence interval, .001-.06). Phylogenetic analysis confirmed these as O. tsutsugamushi strain Boryong. Conclusions: Our study found that 1.6% of patients were coinfected with SFTS and scrub typhus infection. We believe that this information will add a new dimension to clinical diagnosis, which should be considered for better public health management. Further research is needed to better understand the ecological transmission dynamics and geographical distribution of SFTSV and O. tsutsugamushi in endemic countries.

Coxiella burnetii infection in a patient with tick bite.

INTRODUCTION: We report the case of a 60-year-old male who was hospitalized with fever, headache, fatigue, nausea, and myalgia for six days. METHODOLOGY: Polymerase chain reactions (PCR) were performed on patient blood samples, and four ticks were collected from the area the patient mowed. Indirect immunofluorescence assays (IFAs) were performed on serum samples to detect specific antibodies. RESULTS: The collected ticks were identified as Haemaphysalis longicornis. Coxiella species-specific nested PCR (N-PCR) and sequencing confirmed the presence of Coxiella burnetii in the patient, and Coxiella-like bacteria were identified in three of the four ticks. IFA results showed ≥ 4-fold increases in both IgM and IgG antibody titers against Q fever. CONCLUSIONS: Despite positive PCR results for Coxiella species in both the patient and the ticks, different bacterial species were isolated, suggesting that the patient was not infected with C. burnetii through tick bites. Further investigation is required to identify the carriers or transmitters of the infection.

Predicting the severity of postoperative scars using artificial intelligence based on images and clinical data.

Evaluation of scar severity is crucial for determining proper treatment modalities; however, there is no gold standard for assessing scars. This study aimed to develop and evaluate an artificial intelligence model using images and clinical data to predict the severity of postoperative scars. Deep neural network models were trained and validated using images and clinical data from 1283 patients (main dataset: 1043; external dataset: 240) with post-thyroidectomy scars. Additionally, the performance of the model was tested against 16 dermatologists. In the internal test set, the area under the receiver operating characteristic curve (ROC-AUC) of the image-based model was 0.931 (95% confidence interval 0.910‒0.949), which increased to 0.938 (0.916‒0.955) when combined with clinical data. In the external test set, the ROC-AUC of the image-based and combined prediction models were 0.896 (0.874‒0.916) and 0.912 (0.892‒0.932), respectively. In addition, the performance of the tested algorithm with images from the internal test set was comparable with that of 16 dermatologists. This study revealed that a deep neural network model derived from image and clinical data could predict the severity of postoperative scars. The proposed model may be utilized in clinical practice for scar management, especially for determining severity and treatment initiation.

Evaluation of humoral immune response in relation to COVID-19 severity over 1 year post-infection: critical cases higher humoral immune response than mild cases.

Introduction: Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2. We investigated the antibody response against SARS-CoV-2 until 1 year after symptom onset. Methods: We collected 314 serum samples from 97 patients with COVID-19. Antibody responses were tested using an indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), and plaque reduction neutralization test (PRNT) to detect specific neutralizing antibodies. Results: The positivity rates for neutralizing antibodies at a 1:10 titer cutoff were 58.1% at 1 week, 97.8% at 4 weeks, and 78% at 1 year after symptom onset (53.8% in asymptomatic patients and 89.3% in symptomatic patients). The IFA and anti-S1 ELISA IgG results significantly correlated with neutralizing antibody titers. Critical/fatal cases showed significantly higher antibody titers than the asymptomatic or mild-to-moderate illness groups. Nonetheless, the median number of days to the seroconversion of neutralizing antibodies was 10 and 15 in asymptomatic and symptomatic patients, respectively. The asymptomatic group had a significantly higher neutralizing potency index than the mild-to-severe illness groups. Conclusions: Neutralizing antibodies corresponded to earlier seroconversion but had a shorter presence in the asymptomatic group than in the symptomatic group and were still present 1 year after symptom onset in critical/fatal cases.

[Panax notoginseng saponins improve monocrotaline-induced pulmonary arterial hypertension in rats by inhibiting ADAM10/Notch3 signaling pathway].

In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.

Sp1 mediated the inhibitory effect of glutamate on pulmonary surfactant synthesis.

BACKGROUND: Studies have shown that the release of endogenous glutamate (Glu) participates in lung injury by activating N-methyl-D-aspartate receptor (NMDAR), but the mechanism is still unclear. This study was to investigate the effects and related mechanisms of Glu on the lipid synthesis of pulmonary surfactant (PS) in isolated rat lung tissues. METHODS: The cultured lung tissues of adult SD rats were treated with Glu. The amount of [3H]-choline incorporation into phosphatidylcholine (PC) was detected. RT-PCR and Western blot were used to detect the changes of mRNA and protein expression of cytidine triphosphate: phosphocholine cytidylyltransferase alpha (CCTα), a key regulatory enzyme in PC biosynthesis. Western blot was used to detect the expression of NMDAR1, which is a functional subunit of NMDAR. Specific protein 1 (Sp1) expression plasmids were used. After transfected with Sp1 expression plasmids, the mRNA and protein levels of CCTα were detected by RT-PCR and Western blot in A549 cells. After treated with NMDA and MK-801, the mRNA and protein levels of Sp1 were detected by RT-PCR and Western blot in A549 cells. RESULTS: Glu decreased the incorporation of [3H]-choline into PC in a concentration- and time- dependent manner. Glu treatment significantly reduced the mRNA and protein levels of CCTα in lungs. Glu treatment up-regulated NMDAR1 protein expression, and the NMDAR blocker MK-801 could partially reverse the reduction of [3H]-choline incorporation induced by Glu (10-4 mol/L) in lungs. After transfected with Sp1 plasmid for 30 h, the mRNA and protein expression levels of CCTα were increased and the protein expression of Sp1 was also up-regulated. After A549 cells were treated with NMDA, the level of Sp1 mRNA did not change significantly, but the expression of nucleus protein in Sp1 was significantly decreased, while the expression of cytoplasmic protein was significantly increased. However, MK-801could reverse these changes. CONCLUSIONS: Glu reduced the biosynthesis of the main lipid PC in PS and inhibited CCTα expression by activating NMDAR, which were mediated by the inhibition of the nuclear translocation of Sp1 and the promoter activity of CCTα. In conclusion, NMDAR-mediated Glu toxicity leading to impaired PS synthesis may be a potential pathogenesis of lung injury.

SARS-CoV-2 RNAemia and Disease Severity in COVID-19 Patients.

OBJECTIVE: The clinical implications of SARS-CoV-2 RNA viremia in blood (RNAemia) remain uncertain despite gaining more prognostic implications for coronavirus disease 2019 (COVID-19). However, the clinical relevance of SARS-CoV-2 RNAemia has not been well documented. METHODS: We conducted a cohort study on 95 confirmed COVID-19 patients and explored the prospects with evidence of SARS-CoV-2 RNAemia in association with various clinical characteristics. We performed reverse transcription-polymerase chain reaction and studied the risk factors of SARS-CoV-2 RNAemia using logistic regression analysis. RESULTS: The presence of SARS-CoV-2 RNAemia in critical or fatal cases was the highest (66.7%), followed by severe (12.5%) and mild to moderate (1.7%) in admission samples. SARS-CoV-2 viral RNAemia was detected on admission and 1st week samples; however, RNAemia was not detected on the samples collected on the second week post-symptom onset. Multiple regression analysis showed that the severity of the disease was an independent predictor of RNAemia (p < 0.021), and the Kaplan-Meier survival curve estimated an increased mortality rate in SARS-CoV-2 RNAemia cases (p < 0.001). CONCLUSIONS: Our study demonstrated that SARS-CoV-2 RNAemia is a predictive risk factor for clinical severity in COVID-19 patients. Hence, we showed that blood RNAemia might be a critical marker for disease severity and mortality.

HSP70 attenuates neuronal necroptosis through the HSP90α-RIPK3 pathway following neuronal trauma.

BACKGROUND: Necroptosis, a newly defined regulatable necrosis with membrane disruption, has been demonstrated to participate in trauma brain injury (TBI) related neuronal cell death. Heat shock protein 70 (HSP70) is a stress protein with neuroprotective activity, but the potential protective mechanisms are not fully understood. METHODS AND RESULTS: Here, we investigated the effects of HSP70 regulators in a cellular TBI model induced by traumatic neuronal injury (TNI) and glutamate treatment. We found that necroptosis occurred in cortical neurons after TNI and glutamate treatment. Neuronal trauma markedly upregulated HSP70 protein expression within 24 h. The results of immunostaining and lactate dehydrogenase release assay showed that necroptosis following neuronal trauma was inhibited by HSP70 activator TRC051384 (TRC), but promoted by the HSP70 inhibitor 2-phenylethyenesulfonamide (PES). In congruent, the expression and phosphorylation of receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) were differently regulated by HSP70. Furthermore, the expression of HSP90α induced by neuronal trauma was further promoted by PES but decreased by TRC. The data obtained from western blot showed that the phosphorylation of RIPK3 and MLKL induced by HSP70 inhibition were reduced by RIPK3 inhibitor GSK-872 and HSP90α inhibitor geldanamycin (GA). Similarly, inhibition of HSP90α with GA could partially prevented the increased necroptosis induced by PES. CONCLUSIONS: Taken together, HSP70 activation exerted protective effects against neuronal trauma via inhibition of necroptosis. Mechanistically, the HSP90α-mediated activation of RIPK3 and MLKL is involved in these effects.

NMDA receptor activation induces damage of alveolar type II cells and lung fibrogenesis through ferroptosis.

Ferroptosis, a newly discovered type of regulated cell death, has been implicated in numerous human diseases. Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal interstitial lung disease with poor prognosis and limited treatment options. Emerging evidence has linked ferroptosis and glutamate-determined cell fate which is considered a new light on the etiology of pulmonary fibrosis. Here, we observed that N-methyl d-aspartate receptor (NMDAR) activation promoted cell damage and iron deposition in MLE-12 cells in a dose-, time-, and receptor-dependent manner. This mediated substantial Ca2+ influx, upregulated the expression levels of nNOS and IRP1, and affected intracellular iron homeostasis by regulating the expression of iron transport-related proteins (i.e., TFR1, DMT1, and FPN). Excessive iron load promoted the continuous accumulation of total intracellular and mitochondrial reactive oxygen species, which ultimately led to ferroptosis. NMDAR inhibition reduced lung injury and pulmonary fibrosis in bleomycin-induced mice. Bleomycin stimulation upregulated the expression of NMDAR1, nNOS, and IRP1 in mouse lung tissues, which ultimately led to iron deposition via regulation of the expression of various iron metabolism-related genes. NMDAR activation initiated the pulmonary fibrosis process by inducing iron deposition in lung tissues and ferroptosis of alveolar type II cells. Our data suggest that NMDAR activation regulates the expression of iron metabolism-related genes by promoting calcium influx, increasing nNOS and IRP1 expression, and increasing iron deposition by affecting cellular iron homeostasis, ultimately leading to mitochondrial damage, mitochondrial dysfunction, and ferroptosis. NMDAR activation-induced ferroptosis of alveolar type II cells might be a key event to the initiation of pulmonary fibrosis.

Ulinastatin in the treatment of severe acute pancreatitis: A single-center randomized controlled trial.

BACKGROUND: Severe acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract and carries a significant financial burden with high disability and mortality. There are no effective drugs in the clinical management of severe AP, and there is an absence of evidence-based medicine concerning the treatment of severe AP. AIM: To explore whether ulinastatin (UTI) can improve the outcome of severe AP. METHODS: The present research included patients who were hospitalized in intensive critical care units (ICUs) after being diagnosed with severe AP. Patients received UTI (400000 IU) or placebos utilizing computer-based random sequencing (in a 1:1 ratio). The primary outcome measures were 7-d mortality, clinical efficacy, inflammatory response, coagulation function, infection, liver function, renal function, and drug-related adverse effects were evaluated. RESULTS: A total of 181 individuals were classified into two groups, namely, the placebo group (n = 90) and the UTI group (n = 91). There were no statistically significant differences in baseline clinical data between the two groups. The 7-d mortality and clinical efficacy in the UTI group were remarkably improved compared with those in the placebo group. UTI can protect against hyperinflammation and improve coagulation dysfunction, infection, liver function, and renal function. UTI patients had markedly decreased hospital stays and hospitalization expenditures compared with the placebo group. CONCLUSION: The findings from the present research indicated that UTI can improve the clinical outcomes of patients with severe AP and has fewer adverse reactions.

Knowledge mapping of diabetic foot research based on Web of Science database: A bibliometric analysis.

PURPOSE: To take a systematic bibliometric analysis and generate the knowledge mapping of diabetic foot research, basing on big data from Web of Science Core Collection (WoSCC) database. METHODS: Two authors retrieved the WoSCC independently, to obtain publications in field of diabetic foot. CiteSpace was used to detect the co-occurrence relationships of authors, keywords, institutions, and countries/regions, co-citation relationships of authors, references, and journals, and distribution of WoS category. RESULTS: A total of 10,822 documents were included, with 39,541 authors contributed to this field. "Armstrong DG," "Lavery LA," and "Lipsky BA" are the top 3 productive authors, and "Armstrong DG," "Boulton AJM," and "Lavery LA" were most commonly cited. The United States, England and China are the most productive countries, and Univ Washington, Univ Manchester and Harvard Univ published the largest quantity of articles. "Diabetes Care," "Diabetic Med," and "Diabetologia" are the most frequently cited journals, providing the greatest knowledge base. Clustering analysis of keywords co-occurrence map presented the following hotspots: #1 diabetic wound healing, #2 diabetic polyneuropathy, #3 plantar pressure, #4 diabetic foot infection, #5 endovascular treatment, and #6 hyperbaric oxygen therapy. CONCLUSION: This study performed a global overview of diabetic foot research using bibliometric and visualization methods, which would provide helpful references for researchers focusing on this area to capture the future trend.