Chromosome-level genome assembly of the Japanese sawyer beetle Monochamus alternatus.

The Japanese sawyer beetle Monochamus alternatus (Coleoptera: Cerambycidae) is a pest in pine forests and acts as a vector for the pine wood nematode Bursaphelenchus xylophilus, which causes the pine wilt disease. We assembled a high-quality genome of M. alternatus at the chromosomal level using Illumina, Nanopore, and Hi-C sequencing technologies. The assembled genome is 767.12 Mb, with a scaffold N50 of 82.0 Mb. All contigs were assembled into ten pseudo-chromosomes. The genome contains 63.95% repeat sequences. We identify 16, 284 protein-coding genes in the genome, of which 11,244 were functionally annotated. The high-quality genome of M. alternatus provides an invaluable resource for the biological, ecological, and genetic study of this beetle and opens new avenues for understanding the transmission of pine wood nematode by insect vectors.

Identifying the tumor immune microenvironment-associated prognostic genes for prostate cancer.

PURPOSE: This study aimed to explore novel tumor immune microenvironment (TIME)-associated biomarkers in prostate adenocarcinoma (PRAD). METHODS: PRAD RNA-sequencing data were obtained from UCSC Xena database as the training dataset. The ESTIMATE package was used to evaluate stromal, immune, and tumor purity scores. Differentially expressed genes (DEGs) related to TIME were screened using the immune and stromal scores. Gene functions were analyzed using DAVID. The LASSO method was performed to screen prognostic TIME-related genes. Kaplan-Meier curves were used to evaluate the prognosis of samples. The correlation between the screened genes and immune cell infiltration was explored using Tumor IMmune Estimation Resource. The GSE70768 dataset from the Gene Expression Omnibus was used to validate the expression of the screened genes. RESULTS: The ESTIMATE results revealed that high immune, stromal, and ESTIMATE scores and low tumor purity had better prognoses. Function analysis indicated that DEGs are involved in the cytokine-cytokine receptor interaction signaling pathway. In TIME-related DEGs, METTL7B, HOXB8, and TREM1 were closely related to the prognosis. Samples with low expression levels of METTL7B, HOXB8, and TREM1 had better survival times. Similarly, both the validation dataset and qRT-PCR suggested that METTL7B, HOXB8, and TREM1 were significantly decreased. The three genes showed a positive correlation with immune infiltration. CONCLUSIONS: This study identified three TIME-related genes, namely, METTL7B, HOXB8, and TREM1, which correlated with the prognosis of patients with PRAD. Targeting the TIME-related genes might have important clinical implications when making decisions for immunotherapy in PRAD.

Berberine modulates the immunometabolism and differentiation of CD4+ T cells alleviating experimental arthritis by suppression of M1-exo-miR155.

BACKGROUND: The inflammatory cascade mediated by macrophages and T cells is considered to be an important factor in promoting the progression of rheumatoid arthritis (RA). Our previous study found that berberine (BBR) can therapeutically impact adjuvant arthritis (AA) in rats through the regulation of macrophage polarization and the balance of Th17/Treg. However, whether BBR's effects on CD4+T cells response are related to its suppression of M1 macrophage still unclear. PURPOSE: The study aimed to estimate the mechanism of BBR in regulating the immunometabolism and differentiation of CD4+T cells are related to exosome derived from M1-macrophage (M1-exo). STUDY-DESIGN/METHODS: Mice model of collagen-induced arthritis (CIA) was established to investigate the antiarthritic effect of BBR was related with regulation of M1-exo to balance T cell subsets. Bioinformatics analysis using the GEO database and meta-analysis. In vitro, we established the co-culture system involving M1-exo and CD4+ T cells to examine whether BBR inhibits CD4+T cell activation and differentiation by influencing M1-exo-miR155. Exosome was characterized using transmission electron microscopy and western blot analysis, macrophage and CD4+T cell subpopulation were detected by flow cytometry. Further, the metabolic profiles of CD4+T cells were assessed by ECAR, OCR, and the level of glucose, lactate, intracellular ATP. RESULT: BBR reinstates CD4+ T cell homeostasis and reduces miR155 levels in both M1-exo and CD4+ T cells obtained from mice with CIA. In vitro, we found exosomes are indispensable for M1-CM on T lymphocyte activation and differentiation. BBR reversed M1-exo facilitating the activation and differentiation of CD4+T cells. Furthermore, BBR reversed glycolysis reprogramming of CD4+T cells induced by M1-exo, while these regulation effects were significantly weakened by miR155 mimic. CONCLUSION: The delivery of miR-155 by M1-exo contributes to CD4+ T cell immunometabolism dysfunction, a process implicated in the development of RA. The anti-arthritic effect of BBR is associated with the suppression of glycolysis and the disruption of CD4+ T cell subsets balance, achieved by reducing the transfer of M1-exo-miR155 into T cells.

Variation of Ferroptosis-Related Markers in HaCaT Cell Photoaging Models Induced by UVB.

Objective: To investigate the variation of ferroptosis-related markers in HaCaT cell photoaging models induced by ultraviolet-B (UVB). Methods: UVB-treated HaCaT cells served as the model (UVB group) for cellular photoaging, whereas untreated HaCaT cells served as the control group. HaCaT cells were exposed to UVB and the ferroptosis inhibitor Ferrostatin-1 (Fer-1) as part of the UVB+Fer-1 group, and co-cultured with the ferroptosis inducer Erastin as part of the UVB+Erastin group. Reactive oxygen species (ROS) detection kit and senescence-related ß galactosidase (SA-ß-gal) staining were used to evaluate the senescence of HaCaT cells. Lipid reactive oxygen species were detected by C11 BODIPY581/591 probe and mitochondrial morphology was observed by transmission electron microscopy. The mRNA expressions of glutathione peroxidase 4 (GPX4) and ferroptosis-suppressor-protein 1 (FSP1) were detected by real-time reverse transcription-PCR (RT-RCP), and the level of GPX4 protein was measured by immunofluorescence assay. Results: The UVB group had considerably greater levels of ROS, SA-ß-gal, and lipid reactive oxygen species than the control group. The UVB group's mitochondrial volume was reduced, the membrane density increased, and the mitochondrial crest decreased or even disappeared. GPX4 and FSP1 expression levels were similarly found to be lower in the UVB group. Furthermore, the positive rate of SA-ß-gal and lipid reactive oxygen species in the UVB+Fer-1 group was much lower than in the UVB group, but it was reverse in the UVB+Erastin group. This study showed that induced ferroptosis can aggravate aging, and vice versa. Conclusion: According to the findings, ferroptosis may be linked to UVB-induced skin photoaging, which could be attenuated by inhibition of ferroptosis.

Berberine ameliorates collagen-induced arthritis in mice by restoring macrophage polarization via AMPK/mTORC1 pathway switching glycolytic reprogramming.

Dysfunction of macrophage polarization majorly contributes to the progression of rheumatoid arthritis (RA). Polarization and functions of activated macrophages are closely associated with the reprogramming of intracellular metabolisms. Previously, we demonstrated that the anti-arthritis effect of berberine (BBR) in rats with adjuvant-induced arthritis (AA) may be related to AMP-activated protein kinase (AMPK) activation (a key regulator in the biological energy metabolism), and balanced macrophage polarization. However, the specific molecular mechanism of BBR in macrophage metabolism is yet to be elucidated. In this study, we clarified that BBR ameliorated articular inflammation and restored M1/M2 ratio in collagen-induced arthritis (CIA) mice in an AMPK-dependent manner. Mechanistically, BBR reversed the effects of mTORC1 agonist leucine (Leu) on regulating macrophage polarization through activation of AMPK to switch glycolytic reprogramming. Furthermore, BBR inhibition of mTORC1 rely on activation of AMPK to phosphorylate raptor and TSC2 instead of destroying its structure. Our study revealed that the activation of AMPK is required for the BBR-mediated anti-arthritis effect by downregulating mTORC1/HIF-1α and inhibiting the glycolysis in M1 macrophages.

Effects of fungicides on fitness and Buchnera endosymbiont density in Aphis gossypii.

BACKGROUND: Several agricultural fungicides are known to affect insect pests directly and these effects may be transgenerational and mediated through impacts on endosymbionts, providing opportunities for pest control. The cotton aphid Aphis gossypii is a polyphagous pest that can cause large crop yield losses. Here, we tested the effects of three fungicides, pyraclostrobin, trifloxystrobin and chlorothalonil, on the fitness and Buchnera endosymbiont of A. gossypii. RESULTS: The formulations of trifloxystrobin and pyraclostrobin, and the active ingredient of pyraclostrobin produced dose-dependent mortality in A. gossypii, whereas there was no dose-dependent mortality for chlorothalonil. The formulations of trifloxystrobin and pyraclostrobin significantly reduced the lifespan and fecundity of A. gossypii, and increased the density of Buchnera in the parental generation but not the (unexposed) F1 . When the active ingredient of pyraclostrobin was tested, the lifespan of the F0 generation was also reduced, but the density of Buchnera was not, indicating that non-insecticidal chemicals in the fungicide formulation may affect the density of the endosymbiont of A. gossypii. There was no transgenerational effect of the active ingredient of pyraclostrobin on the lifespan and Buchnera of (unexposed) F1 . CONCLUSIONS: Our results suggest that formulations of two strobilurin fungicides have immediate impacts on the fitness of A. gossypii, and chemicals in the formulation impact the density of the primary Buchnera endosymbiont. Our study highlights the potential effects of non-insecticidal chemicals of fungicides on aphid pests and their primary endosymbionts but direct connections between fitness and Buchnera densities remain unclear. © 2023 Society of Chemical Industry.

Host-plant adaptation in xylophagous insect-microbiome systems: Contributionsof longicorns and gut symbionts revealed by parallel metatranscriptome.

Adaptation to host plants is of great significance in the ecology of xylophagous insects. The specific adaptation to woody tissues is made possible through microbial symbionts. We investigated the potential roles of detoxification, lignocellulose degradation, and nutrient supplementation of Monochamus saltuarius and its gut symbionts in host plant adaptation using metatranscriptome. The gut microbial community structure of M. saltuarius that fed on the two plant species were found to be different. Plant compound detoxification and lignocellulose degradation genes have been identified in both beetles and gut symbionts. Most differentially expressed genes associated with host plant adaptations were up-regulated in larvae fed on the less suitable host (Pinus tabuliformis) compared to larvae fed on the suitable host (Pinus koraiensis). Our findings indicated that M. saltuarius and its gut microbes respond to plant secondary substances through systematic transcriptome responses, allowing them to adapt to unsuitable host plants.

Transcutaneous electrical cranial-auricular acupoint stimulation versus escitalopram for mild-to-moderate depression: An assessor-blinded, randomized, non-inferiority trial.

AIM: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An assessor-blinded, randomized, non-inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild-to-moderate major depressive disorder. METHODS: 468 participants received two TECAS sessions per day at home (n = 233) or approximately 10-13 mg/day escitalopram (n = 235) for 8 weeks plus 4-week follow-up. The primary outcome was clinical response, defined as a baseline-to-endpoint ≥50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality. RESULTS: The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval [CI], -5.9% to 12.9%) in intention-to-treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, -6.9% to 11.4%) in per-protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non-inferiority margin of -10% (P ≤ 0.004 for non-inferiority). Most secondary outcomes did not differ between the two groups. TECAS-treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% vs 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram. CONCLUSIONS: TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma-associated depression. It could serve an effective portable therapy for mild-to-moderate depression.

Two new alkaloids produced by Dothideomycetes sp. BMC-101 isolated from the Magnolia grandiflora.

AbstactA total of 16 fungal strains were isolated from fresh leaves and flowers of Magnolia grandiflora and the EtOAc extracts of them were assayed for antitumor activities. Among these, the fungus Dothideomycetes sp. BMC-101 with broad spectrum inhibition was selected for further study. Four alkaloids (1-4) including two new compounds (2-(hydroxyimino)-3-phenylpropanoyl)-L-phenylalanine (1) and 8-Acetyl-bisdethiobis(methylsulfanyl)apoaranotin (4)) were isolated from Dothideomycetes sp. BMC-101. The structure of 1 was characterized with an oxime moiety formed by the condensation of two phenylalanines. To our knowledge, this is the first report on a fungal phenylalanine derivative with an oxime moiety.

Minocycline, a classic antibiotic, exerts psychotropic effects by normalizing microglial neuroinflammation-evoked tryptophan-kynurenine pathway dysregulation in chronically stressed male mice.

The dysregulation of tryptophan-kynurenine pathway (TKP) is extensively involved in the pathophysiology of Alzheimer's disease, depression, and neurodegenerative disorders. Minocycline, a classic antibiotic, may exert psychotropic effects associated with the modulation of TKP. In this study, we examined the effects of minocycline in improving behaviour and modulating TKP components in chronically stressed male mice. Following repeated treatment with 22.5 mg/kg and 45 mg/kg minocycline for 27 days, the stressed mice particularly with higher dose displayed significant improvement on cognitive impairment, depression- and anxiety-like behaviour. Minocycline suppressed stress-induced overexpression of pro-inflammatory cytokines and restored anti-inflammatory cytokines. Chronic stress dramatically suppressed blood and prefrontal cortical levels of the primary substrate tryptophan (TRP), the neuroprotective metabolite kynurenic acid (KYNA), and KYNA/KYN ratio, but increased the intermediate kynurenine (KYN), 3-hydroxykynurenine (3-HK), KYN/TRP ratio, and the neurotoxic metabolite quinolinic acid (QUIN). Minocycline partially or completely reversed changes in these components. Minocycline also inhibited stress-induced overexpression of QUIN-related enzymes, indoleamine 2, 3-dioxygenase 1(iDO-1), kynureninase (KYNU), kynurenine 3-monooxygenase (KMO), 3-hydroxyanthranilate 3,4-dioxygenase (3-HAO), but rescued the decreased expression of kynurenine aminotransferase (KAT) in brain regions. Behavioral improvements were correlated with multiple TKP metabolites and enzymes. These results suggest that the psychotropic effects of minocycline are mainly associated with the restoration of biodistribution of the primary substrate in the brain and normalization of neuroinflammation-evoked TKP dysregulation.

Cradle for the newborn Monochamus saltuarius: Microbial associates to ward off entomopathogens and disarm plant defense.

The Japanese pine sawyer, Monochamus saltuarius, as a beetle vector of Bursaphelenchus xylophilus (pine wood nematode), is an economically important forest pest in Eurasia. To feed on the phloem and xylem of conifers, M. saltuarius needs to overcome various stress factors, including coping with entomopathogenic bacteria and also various plant secondary compounds (PSCs). As an important adaptation strategy to colonize host trees, M. saltuarius deposit eggs in oviposition pits to shield their progeny. These pits harbor bacterial communities that are involved in the host adaptation of M. saltuarius to the conifers. However, the composition, origin, and functions of these oviposition pit bacteria are rarely understood. In this study, we investigated the bacterial community associated with M. saltuarius oviposition pits and their ability to degrade PSCs. Results showed that the bacterial community structure of M. saltuarius oviposition pits significantly differed from that of uninfected phloem. Also, the oviposition pit bacteria were predicted to be enriched in PSC degradation pathways. The microbial community also harbored a lethal strain of Serratia, which was significantly inhibited. Meanwhile, metatranscriptome analysis indicated that genes involved in PSCs degradation were expressed complementarily among the microbial communities of oviposition pits and secretions. In vitro degradation showed that bacteria cultured from oviposition pits degraded more monoterpenes and flavonoids than bacteria cultured from uninfected phloem isolates. Disinfection of oviposition pits increased the mortality of newly hatched larvae and resulted in a significant decrease in body weight in the early stages. Overall, our results reveal that M. saltuarius construct oviposition pits that harbor a diverse microbial community, with stronger PSCs degradation abilities and a low abundance of entomopathogenic bacteria, resulting in the increased fitness of newly hatched larvae.

miR-519d-3p alleviates high glucose-induced human retinal microvascular endothelial cells dysfunction and inhibits angiogenesis by targeting hypoxia inducible factor 1 subunit alpha / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To clarify the effect of miR-519d-3p on high glucose-induced human retinal microvascular endothelial cells(HRMEC)dysfunction and angiogenesis, and to elucidate the regulatory mechanism of miR-519d-3p on hypoxia inducible factor 1 subunit alpha(HIF-1α).METHODS: The normal glucose(NG)and high glucose(HG)cell models were established by inducing HRMEC with 5 and 30 mmol/L glucose, respectively. Control group: HG cell model was transfected with negative control mimics; mannitol group: the control group was added with 25 mmol/L mannitol; miR-519d-3p overexpression group: HG cell model was transfected with miR-519d-3p mimics; miR-519d-3p combined with HIF-1α overexpression group: HG cell model was co-transfected with miR-519d-3p mimics and HIF-1α overexpression vector. The expression of miR-519d-3p in each group was tested by real-time fluorescence quantitative PCR. The expression of HIF-1α protein in each group was tested by Western blotting. The binding sites between miR-519d-3p and HIF-1α were detected by luciferase reporter gene assay. The cell proliferation of each group was detected by CCK-8. The cell apoptosis of each group was tested by Hoechst 33342 staining. The protein expression of extracellular fluid inflammatory factors tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in each group was tested by ELISA. The formation of new capillary lumen-like structures was detected by tubule formation assay.RESULTS: Compared with the NG, miR-519d-3p expression was significantly reduced in the HG cell model, while HIF-1α protein expression was significantly increased in the HG(all P<0.01). Compared with the control group, HIF-1α protein expression was significantly reduced in the miR-519d-3p overexpression group(P<0.01). The “CGUGAAA” sequence of miR-519d-3p could specifically bind to the “GCACUUU” sequence of HIF-1α 3'-untranslated region(3'-UTR). Compared with the control group, the miR-519d-3p overexpression group showed a significant increase in 24, 48 and 72h absorbance values, a significant decrease in cell apoptotic rate, a significant decrease in the concentrations of TNF-α, IL-1β and IL-6, and a significant decrease in the number of new capillary lumen-like structures(all P<0.01). Compared with the miR-519d-3p overexpression group, the miR-519d-3p combined with HIF-1α overexpression group showed a significant decrease in 24, 48 and 72h absorbance values, a significant increase in cell apoptotic rate, a significant increase in the concentrations of TNF-α, IL-1β and IL-6, and a significant increase in the number of new capillary lumen-like structures(all P<0.01). There was no difference between the control group and mannitol group in the comparison of the above indicators(all P>0.05).CONCLUSION: miR-519d-3p expression is down-regulated while HIF-1α protein expression is up-regulated in high glucose induced HRMEC model. HIF-1α is a target gene of miR-519d-3p. The miR-519d-3p targets HIF-1α to increase cell proliferation and reduce cell apoptosis and inflammation, thereby alleviating high glucose-induced HRMEC dysfunction and inhibiting angiogenesis.

Exploration of family rehabilitation model for children with scar contracture after hand burns / 中华烧伤杂志

Objective: To explore the family rehabilitation model for children with scar contracture after hand burns and observe its efficacy. Methods: A retrospective non-randomized controlled study was conducted. From March 2020 to March 2021, 30 children with scar contracture after deep partial-thickness to full-thickness burns of hands, who met the inclusion criteria, were hospitalized in the Burn Center of PLA of the First Affiliated Hospital of Air Force Medical University. According to the rehabilitation model adopted, 18 children (23 affected hands) were included in a group mainly treated by family rehabilitation (hereinafter referred to as family rehabilitation group), and 12 children (15 affected hands) were included in another group mainly treated by hospital rehabilitation (hereinafter referred to as hospital rehabilitation group). In the former group, there were 11 males and 7 females, aged (4.8±2.1) years, who began rehabilitation treatment (3.1±0.8) d after wound healing; in the latter group, there were 7 males and 5 females, aged (4.6±2.1) years, who began rehabilitation treatment (2.8±0.7) d after wound healing. The children in hospital rehabilitation group mainly received active and passive rehabilitation training in the hospital, supplemented by independent rehabilitation training after returning home; after 1-2 weeks of active and passive rehabilitation training in the hospital, the children in family rehabilitation group received active and passive rehabilitation training at home under the guidance of rehabilitation therapists through WeChat platform. Both groups of children were treated for 6 months. During the treatment, they wore pressure gloves and used hand flexion training belts and finger splitting braces. Before treatment and after 6 months of treatment, the modified Vancouver scar scale, the total active movement of the hand method, and Carroll quantitative test of upper extremity function were used to score/rate the scar of the affected hand (with the difference of scar score between before treatment and after treatment being calculated), the joint range of motion (with excellent and good ratio being calculated), and the function of the affected limb, respectively. Data were statistically analyzed with independent sample t test, equivalence test, Fisher's exact probability test, and Mann-Whitney U test. Results: The differences of scar scores of the affected hands of children in family rehabilitation group and hospital rehabilitation group between after 6 months of treatment and those before treatment were 3.0 (2.0, 7.0) and 3.0 (2.0, 8.0) respectively (with 95% confidence interval of 2.37-5.38 and 1.95-5.91). The 95% confidence interval of the difference between the differences of the two groups was -2.43-2.21, which was within the equivalent boundary value of -3-3 (P<0.05). The excellent and good ratios of joint range of motion of the affected hand of children in family rehabilitation group and hospital rehabilitation group were 3/23 and 2/15 respectively before treatment, and 15/23 and 12/15 respectively after 6 months of treatment. The ratings of joint range of motion of the affected hand of children in family rehabilitation group and hospital rehabilitation group after 6 months of treatment were significantly higher than those before treatment (with Z values of 3.58 and 2.30, respectively, P<0.05), but the ratings of joint range of motion of the affected hand between the two groups were similar before treatment and after 6 months of treatment (with Z values of 0.39 and 0.55, respectively, P>0.05). The functional ratings of the affected limbs of children in family rehabilitation group and hospital rehabilitation group after 6 months of treatment were significantly higher than those before treatment (with Z values of 3.98 and 3.51, respectively, P<0.05), but the functional ratings of the affected limbs between the two groups were similar before treatment and after 6 months of treatment (with Z values of 1.27 and 0.38, respectively, P>0.05). Conclusions: The WeChat platform assisted rehabilitation treatment with mainly family rehabilitation, combined with hand flexion and extension brace can effectively reduce the scarring after children's hand burns, improve the joint range of motion of the affected hands, and promote the recovery of affected limb function. The effect is similar to that of hospital-based rehabilitation providing an optional rehabilitation, treatment method for children who cannot continue to receive treatment in hospital.

Development and validation of a risk prediction score for the severity of acute hypertriglyceridemic pancreatitis in Chinese patients.

BACKGROUND: The frequency of acute hypertriglyceridemic pancreatitis (AHTGP) is increasing worldwide. AHTGP may be associated with a more severe clinical course and greater mortality than pancreatitis caused by other causes. Early identification of patients with severe inclination is essential for clinical decision-making and improving prognosis. Therefore, we first developed and validated a risk prediction score for the severity of AHTGP in Chinese patients. AIM: To develop and validate a risk prediction score for the severity of AHTGP in Chinese patients. METHODS: We performed a retrospective study including 243 patients with AHTGP. Patients were randomly divided into a development cohort (n = 170) and a validation cohort (n = 73). Least absolute shrinkage and selection operator and logistic regression were used to screen 42 potential predictive variables to construct a risk score for the severity of AHTGP. We evaluated the performance of the nomogram and compared it with existing scoring systems. Last, we used the best cutoff value (88.16) for severe acute pancreatitis (SAP) to determine the risk stratification classification. RESULTS: Age, the reduction in apolipoprotein A1 and the presence of pleural effusion were independent risk factors for SAP and were used to construct the nomogram (risk prediction score referred to as AAP). The concordance index of the nomogram in the development and validation groups was 0.930 and 0.928, respectively. Calibration plots demonstrate excellent agreement between the predicted and actual probabilities in SAP patients. The area under the curve of the nomogram (0.929) was better than those of the Bedside Index of Severity in AP (BISAP), Ranson, Acute Physiology and Chronic Health Evaluation (APACHE II), modified computed tomography severity index (MCTSI), and early achievable severity index scores (0.852, 0.825, 0.807, 0.831 and 0.807, respectively). In comparison with these scores, the integrated discrimination improvement and decision curve analysis showed improved accuracy in predicting SAP and better net benefits for clinical decisions. Receiver operating characteristic curve analysis was used to determine risk stratification classification for AHTGP by dividing patients into high-risk and low-risk groups according to the best cutoff value (88.16). The high-risk group (> 88.16) was closely related to the appearance of local and systemic complications, Ranson score ≥ 3, BISAP score ≥ 3, MCTSI score ≥ 4, APACHE II score ≥ 8, C-reactive protein level ≥ 190, and length of hospital stay. CONCLUSION: The nomogram could help identify AHTGP patients who are likely to develop SAP at an early stage, which is of great value in guiding clinical decisions.

Hirudin alleviates acute ischemic stroke by inhibiting NLRP3 inflammasome-mediated neuroinflammation: In vivo and in vitro approaches.

Acute ischemic stroke is a severe condition that a vessel supplying blood to the brain is abruptly blocked mostly due to cerebral thrombosis and embolism. There is a dearth of the effective prevention and early intervention strategies. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation plays a crucial role in the pathophysiology of ischemic stroke. Hirudin is a secretion from the salivary glands of the leech Hirudo medicinalis and has a role in regulating inflammation. In this study, hirudin with a dose of 10-40 mg/kg was given to middle cerebral artery occlusion/reperfusion mice. Hirudin markedly constrained cerebral infarct area in a dose-dependent manner, and significantly improved locomotor disability at 40 mg/kg dose. Similar to MCC950, a selective NLRP3 inflammasome inhibitor, hirudin inhibited M1 polarization and promoted M2 polarization. It also strikingly suppressed the ischemia-induced overexpression of NLRP3 and its downstream components, caspase-1, apoptosis-associated speck-like protein (ASC), and interleukin-1ß (IL-1ß). Hirudin and MCC950 equivalently protected viability and death of BV-2 microglia cells against oxygen-glucose deprivation/reperfusion (OGD/R), an in vitro cell model of brain ischemia. Both agents had similar effects in normalizing the OGD/R-evoked aberrant microglial profiles and NLRP3 pathway dysregulation as observed in the mice. These results demonstrated anti-ischemic effects of hirudin and its association with the inhibition of microglial NLRP3 inflammasome-mediated neuroinflammation. Hirudin is a promising agent for the early intervention of acute ischemic stroke.

Mechanism of Ba Zhen Tang Delaying Skin Photoaging Based on Network Pharmacology and Molecular Docking.

Purpose: To study the efficacy of Ba Zhen Tang in delaying skin photoaging and its potential mechanism based on network pharmacology and molecular docking. Methods: First, we screened the active components and targets of Ba Zhen Tang by Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and The Universal Protein Resource (UniProt). The target genes of skin photoaging were obtained from GeneCards and GeneMap database. Then, we analyzed the protein-protein interaction (PPI) by STRING database. The network map was constructed by Cytoscape. Finally, we performed Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis by Metascape database. The molecular docking via Autodock Vina and Pymol. Furthermore, skin photoaging cellular models were established, and the effects of Ba Zhen Tang on ameliorating skin photoaging were investigated. Results: A total of 160 active ingredients in Ba Zhen Tang and 60 targets of Ba Zhen Tang for delaying skin photoaging were identified. By GO enrichment analysis, 1153 biological process entries, 45 cellular component entries and 89 molecular functional entries were obtained. A total of 155 signal pathways were obtained by KEGG analysis. Ba Zhen Tang is related to MAPK signaling pathway, TNF signaling pathway and AGE-RAGE signaling pathway in diabetic complications, etc., which directly affect the key nodes of photoaging. The molecular docking results showed that there was a certain affinity between the main compounds (kaempferol, quercetin, ß-sitosterol, naringenin) and core target genes (PTGS2, CASP3, MAPK1, MAPK3, TP53). Ba Zhen Tang-treated mouse serum inhibited the senescence and p16INK4a expression of human immortalized keratinocyte (HaCaT) cells irradiated by ultraviolet-B (UVB). Conclusion: Our study elucidated the potential pharmacological mechanism of Ba Zhen Tang in the treatment of photoaging through multiple targets and pathways. The therapeutic effects of Ba Zhen Tang on skin photoaging were validated in cellular models.

A network pharmacology-based study of the potential targets and mechanisms of action of Qibao Meiran Dan in delaying skin aging.

OBJECTIVE: The aim of this study was to use network pharmacology to explore the potential targets and mechanisms of action of Qibao Meiran Dan in relation to delaying skin aging. METHODS: The traditional Chinese medicine systems pharmacology database and analysis platform, and the traditional Chinese medicine integrated database, were used to screen the active ingredients and targets of Qibao Meiran Dan. The human gene database GeneCards and the gene database of the National Center for Biotechnology Information were jointly adopted to obtain skin aging-related target genes. The search tool for the retrieval of interacting genes/proteins (STRING) database was used for core analysis of protein-protein interaction. RESULTS: In total, 72 effective active ingredients, 273 action targets, 234 skin aging target genes, and 64 intersecting core targets were identified. GO enrichment analysis provided 393 biological process entries, and the KEGG analysis was represented by the tumor necrosis factor (TNF) signaling pathway, where the core targets of TNF-α and matrix metalloproteinase-1 (MMP-1) were enriched. The experimental results showed that cell morphology was clearer and more refractive in the Qibao Meiran Dan group than in the model group. CONCLUSION: Qibao Meiran Dan may regulate oxidative stress injury and collagen metabolism by downregulating the expression of TNF-α and MMP-1, thus slowing skin aging.

Cassane diterpenoids from Caesalpinia pulcherrima and their anti-inflammatory and α-glycosidase inhibitory activities.

Three undescribed cassane-type diterpenoids (CAs), caesalpulcherrins K-M (1-3), together with three known ones (4-6) were isolated from the aerial parts of Caesalpinia pulcherrima (L.) Sw (Fabaceae). Their structures were elucidated via analysis of NMR (1 D and 2 D) and HRESIMS data. The character for caesalpulcherrin K possessing the olefin bond at C-11 and C-12 in its cassane skeleton was observed, which belonged to a small group among more than 450 CAs. That is, only fifteen derivatives have been reported up to now, to our knowledge. Biological evaluation revealed that compounds 1-6 exhibited moderate anti-inflammatory activity, with an IC50 value from 6.04 ± 0.34 to 8.92 ± 0.65 µM. Furthermore, compounds 5 and 6 exhibited significant α-glucosidase inhibitory activity at 10 µM.

Two new benzophenone glycosides from the aerial parts of Hypericum przewalskii.

Plants of the genus Hypericum contain various types of secondary metabolites that exhibited extensive biological activities. In the ongoing efforts to discover natural neuroinflammatory inhibitors with the potential to develop into therapeutic agents for neurodegenerative diseases, two new benzophenone glycosides, hyperewalones A and B (1 and 2), along with eight known compounds (3-10), were isolated from the aerial parts of Hypericum przewalskii. Their structures were elucidated by comprehensive analysis of IR, HRESIMS, 1D and 2D NMR spectra, and chemical derivatization. The anti-neuroinflammatory activity of compounds 1-10 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated BV-2 microglial cells. Compounds 2, 4, 6-8 exhibited significant anti-neuroinflammatory activity with IC50 values of 0.61-4.90 µM. These findings suggest that the benzophenone, ionone, and flavonoid glycosides isolated from H. przewalskii are promising anti-neuroinflammatory compounds worthy of further investigations.

The genus Alcochera Frster (Hymenoptera, Ichneumonidae, Ctenopelmatinae) in China with a key to world species.

Two new species of Alcochera (Ichneumonidae, Ctenopelmatinae, Mesoleiini), Alcochera flavoclypeata Sheng Sun, sp. nov. collected from Labagoumen Natural Reserve, Huairou, Beijing, and A. truncata Sheng Sun, sp. nov. from Wugongshan Natural Reserve, are described and illustrated. An updated taxonomic key to world species of Alcochera is provided.