Cobrotoxin from Naja naja atra

Chronic kidney disease (CKD) becomes a global health problem with high morbidity and mortality. Adriamycin- (ADR-) induced rodent chronic nephropathy is a classic experimental model of human minimal lesion nephrotic syndrome. The present study investigated the effect of cobrotoxin (CTX) on ADR-induced nephropathy. Rats were given 6 mg/kg ADR once through the tail vein to replicate ADR nephropathy model. CTX was administered to rats daily by placing a fast dissolving CTX membrane strip under the tongue starting from 5 days prior to ADR administration until the end of experiment. The results showed that CTX ameliorated the symptoms of ADR nephropathy syndrome with reduced body weight loss, proteinuria, hypoalbuminemia, dyslipidemia, serum electrolyte imbalance, oxidative stress, renal function abnormities, and kidney pathological lesions. Anti-inflammatory cytokine IL-10 expression was elevated after CTX administration in ADR nephropathy model. CTX inhibited the phosphorylation of IκB-α and NF-κB p65 nuclear translocation. Meanwhile, CTX upregulated the protein level of podocyte-specific nephrin and downregulated the level of fibrosis-related TGF-β. These findings suggest that CTX may be a potential drug for chronic kidney diseases

Solitary Necrotic Nodule of the Liver: A Report of Two Cases and Review of the Literature

To investigate the clinicopathological characteristics and possible causes of solitary necrotic nodule of the liver (SNN), two cases of SNN of the liver were studied with clinicopathological data, immunohistochemistry, and histochemistry staining. The patients had no specific symptoms, with negative results for the serum tumor markers. CT and ultrasound all showed low-density lesion. Morphologically, there was isolate, single necrosis tubercle of the liver. It was composed of a central necrotic core and a peripheral fibrotic capsule with inflammatory cells, including histiocytes, plasma cells, lymphocytes, and so forth. The staining result of PAS, acid-fast, and iron was all negative, and AG + VG staining showed that the outline of reticular fibers and collagen was intact. Vimtin was positive for necrotic tissue and surrounding fibrous tissue. CD34 and CD68 was both positive for case 1. CK was negative in case 2 but positive for a few residual cells in case 1. SNN of the liver is a rare nonmalignant disease with a good prognosis. Hemangioma and fatty liver might be ones of the causes of SNN

A culture of conservation: How an ancient forest plantation turned into an old-growth forest reserve – The story of the Wamulin forest

The global expansion of forest plantations at the expense of natural forests, especially old-growth forests, raises concerns about habitat loss and a decline in ecosystem services. Natural regeneration of second-growth forests with minimal human assistance has been suggested as a cost-effective way to restore forests and increase forest ecosystem service potential. However, it is unclear whether natural regeneration will lead to the development of second-growth forests similar to natural forests because most naturally regenerated second-growth forests are still young. We present a case study of a very old second-growth forest in southeastern China in which a forest plantation established approximately six centuries ago has now developed into an old forest with extraordinary high biodiversity levels, an immense carbon pool, and a rich culture. The forest was established in the 14th century because of a charitable contribution, became protected under the Chinese cultural norm of ‘unity between humans and the nature’, and was conserved because of the belief that the prosperity of people is closely linked to the prosperity of trees. The recent designation of the forest as a nature reserve further protects it from development despite competing land-use demands related to recent economic growth. This case illustrates that, although human activity is the main cause for the disappearance and degradation of many forests, when human interests and cultural values align second-growth restoration and subsequent forest conservation can lead to the successional development of old-growth forests. Because this development takes multiple centuries, the protection of current second-growth forests within conservation easements (e.g. nature reserves) and the reformation of culture values for the linkage of forests to human well-being are key aspects of the continued conservation-aided succession of second-growth forests. A free Plain Language Summary can be found within the Supporting Information of this article

Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by Orally Administrated Cardiotoxin from Naja naja atra

Previous studies reported the oral administration of Naja naja atra venom (NNAV) reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight) via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180 μg/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease

A New Security Evaluation Method Based on Resultant for Arithmetic-Oriented Algorithms

The rapid development of advanced cryptographic applications like multi-party computation (MPC), fully homomorphic encryption (FHE), and zero-knowledge (ZK) proofs have motivated the designs of the so-called arithmetic-oriented (AO) primitives. Efficient AO primitives typically build over large fields and use large S-boxes. Such design philosophy brings difficulties in the cryptanalysis of these primitives as classical cryptanalysis methods do not apply well. The generally recognized attacks against these primitives are algebraic attacks, especially Groebner basis attacks. Thus, the numbers of security rounds are usually derived through the complexity of solving the system of algebraic equations using Groebner bases. In this paper, we propose a novel framework for algebraic attacks against AO primitives. Instead of using Groebner basis, we use resultants to solve a system of multivariate equations that can better exploit the algebraic structures of AO primitives. We employ several techniques to reduce the dimensions of the resultants and avoid rapid increases in degrees, including meet-in-the-middle modeling, variable substitutions, and fast Lagrange interpolation. We apply our attack to three mainstream AO cryptographic primitives: Rescue-Prime, Anemoi, and Jarvis. For Rescue-Prime, we theoretically prove that the final univariate equation has a degree of at most a specific power of three and practically attack five rounds for the first time. We attack the full-round of Anemoi with complexity 2^110.10, which has been claimed to provide 127 bits of security. We also give the first practical attack against eight rounds of Anemoi over a 55-bit prime field. For Jarvis, we improve the existing practical attack by a factor of 100. Therefore, we point out that our analysis framework can be used as a new evaluation method for AO designs

MHC-I promotes apoptosis of GABAergic interneurons in the spinal dorsal horn and contributes to cancer induced bone pain

Cancer induced bone pain (CIBP) remains one of the most intractable clinical problems due to poor understanding of its underlying mechanisms. Recent studies demonstrate the decline of inhibitory interneurons, especially GABAergic interneurons in the spinal cord, can evoke generation of chronic pain. It has also been reported that neuronal MHC-I expression renders neurons vulnerable to cytotoxic CD8+ T cells and finally lead to neurons apoptosis in a variety neurological disorders. However, whether MHC-I could induce the apoptosis of GABAergic interneurons in spinal cord and contribute to the development of CIBP remains unknown. In this study, we investigated roles of MHC-I and underlying mechanisms in CIBP on a rat model. Our results showed that increased MHC-I expression on GABAergic interneurons could deplete GABAergic interneurons by inducing their apoptosis in the spinal dorsal horn of tumor-bearing rats. Pretreatment of MHC-I RNAi-lentivirus could prevent the apoptosis of GABAergic interneurons and therefore alleviated mechanical allodynia induced by tumor cells intratibial injection. Additionally, we also found that CD8+ T cells were colocalized with MHC-I and GABAergic neurons and presented a significant and persistent increase in the spinal cord of tumor-bearing rats. Taken together, these findings indicated that MHC-I could evoke CIBP by promoting apoptosis of GABAergic interneurons in the dorsal horn, and this apoptosis was closely related to local CD8+ T cells

Loop-mediated isothermal amplification (LAMP): Early detection of Toxoplasma gondii infection in mice

<p>Abstract</p> <p>Background</p> <p>Toxoplasmosis is a widespread zoonotic parasitic disease that occurs in both animals and humans. Traditional molecular assays are often difficult to perform, especially for the early diagnosis of <it>Toxoplasma gondii </it>infections. Here, we established a novel loop-mediated isothermal amplification targeting the 529 bp repeat element (<it>529 bp</it>-LAMP) to detect <it>T. gondii </it>DNA in blood samples of experimental mice infected with tachyzoites of the RH strain.</p> <p>Findings</p> <p>The assay was performed with Bst DNA polymerase at 65°C for 1 h. The detection limit of the <it>529 bp-</it>LAMP assay was as low as 0.6 fg of <it>T. gondii </it>DNA. The sensitivity of this assay was 100 and 1000 fold higher than that of the LAMP targeting <it>B1 </it>gene (<it>B1</it>-LAMP) and nested PCR targeting 529 bp repeat element (<it>529 bp</it>-nested PCR), respectively. The specificity of the <it>529 bp-</it>LAMP assay was determined using the DNA samples of <it>Trypanosoma evansi, Plasmodium falciparum, Paragonimus westermani, Schistosoma japonicum, Fasciola hepatica </it>and <it>Angiostrongylus cantonensis</it>. No cross-reactivity with the DNA of any parasites was found. The assay was able to detect <it>T. gondii </it>DNA in all mouse blood samples at one day post infection (dpi).</p> <p>Conclusions</p> <p>We report the following findings: (<it>i</it>) The detection limit of the <it>529 bp-</it>LAMP assay is 0.6 fg of <it>T. gondii </it>DNA; (<it>ii</it>) The assay does not involve any cross-reactivity with the DNA of other parasites; (<it>iii</it>) This is the first report on the application of the LAMP assay for early diagnosis of toxoplasmosis in blood samples from experimentally infected mice. Due to its simplicity, sensitivity and cost-effectiveness for common use, we suggest that this assay should be used as an early diagnostic tool for health control of toxoplasmosis.</p

Experimental and Theoretical Study of Surface-Enhanced Raman Spectra of Sulfadiazine Adsorbed on Nanoscale Gold Colloids.

Sulfadiazine, as a class of antibiotics, has been widely used in the world for decades; however, its surface-enhanced Raman spectra (SERS) on gold colloids are obviously different from ordinary Raman spectra in the solid powder and liquid solution. To explore the reasons for such significant differences, we used density functional theory calculations and normal-mode analysis to investigate the effects of the configuration, conformation, protonation, hydrogen-bonding interaction, and adsorption configurations of sulfadiazine on gold clusters to check these different effects on the vibrational assignments. Our calculated results can be summarized as two points. First, the Raman spectra strongly depend on the configuration, conformation, protonation, and hydrogen bonding of sulfadiazine. Second, the wagging vibration displays a significant vibrational frequency shift and a very strong SERS peak responsible for the observed SERS signal when sulfadiazine is adsorbed on gold clusters through the terminal amino group. This is different from another adsorption configuration through two oxygen atoms of the -SO2NH- group on gold clusters. Finally, we further investigate the potential energy surfaces along the wagging vibration and the binding interaction of -NH2 adsorbed on different sites of gold surfaces

Intelligent diagnostic model for pterygium by combining attention mechanism and MobileNetV2

AIM: To evaluate the application of an intelligent diagnostic model for pterygium. METHODS: For intelligent diagnosis of pterygium, the attention mechanisms—SENet, ECANet, CBAM, and Self-Attention—were fused with the lightweight MobileNetV2 model structure to construct a tri-classification model. The study used 1220 images of three types of anterior ocular segments of the pterygium provided by the Eye Hospital of Nanjing Medical University. Conventional classification models—VGG16, ResNet50, MobileNetV2, and EfficientNetB7—were trained on the same dataset for comparison. To evaluate model performance in terms of accuracy, Kappa value, test time, sensitivity, specificity, the area under curve (AUC), and visual heat map, 470 test images of the anterior segment of the pterygium were used. RESULTS: The accuracy of the MobileNetV2+Self-Attention model with 281 MB in model size was 92.77%, and the Kappa value of the model was 88.92%. The testing time using the model was 9ms/image in the server and 138ms/image in the local computer. The sensitivity, specificity, and AUC for the diagnosis of pterygium using normal anterior segment images were 99.47%, 100%, and 100%, respectively; using anterior segment images in the observation period were 88.30%, 95.32%, and 96.70%, respectively; and using the anterior segment images in the surgery period were 88.18%, 94.44%, and 97.30%, respectively. CONCLUSION: The developed model is lightweight and can be used not only for detection but also for assessing the severity of pterygium

Biomarkers for Early Diagnostic of Mild Cognitive Impairment in Type-2 Diabetes Patients: A Multicentre, Retrospective, Nested Case–Control Study

AbstractBackgroundBoth type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are common age-associated disorders and T2DM patients show an increased risk to suffer from AD, however, there is currently no marker to identify who in T2DM populations will develop AD. Since glycogen synthase kinase-3β (GSK-3β) activity, ApoE genotypes and olfactory function are involved in both T2DM and AD pathogenesis, we investigate whether alterations of these factors can identify cognitive impairment in T2DM patients.MethodsThe cognitive ability was evaluated using Minimum Mental State Examination (MMSE) and Clinical Dementia Rating (CDR), and the mild cognitive impairment (MCI) was diagnosed by Petersen's criteria. GSK-3β activity in platelet, ApoE genotypes in leucocytes and the olfactory function were detected by Western/dot blotting, the amplification refractory mutation system (ARMS) PCR and the Connecticut Chemosensory Clinical Research Center (CCCRC) test, respectively. The odds ratio (OR) and 95% confidence intervals (95% CI) of the biomarkers for MCI diagnosis were calculated by logistic regression. The diagnostic capability of the biomarkers was evaluated by receiver operating characteristics (ROC) analyses.FindingsWe recruited 694 T2DM patients from Jan. 2012 to May. 2015 in 5 hospitals (Wuhan), and 646 of them met the inclusion criteria and were included in this study. 345 patients in 2 hospitals were assigned to the training set, and 301 patients in another 3 hospitals assigned to the validation set. Patients in each set were randomly divided into two groups: T2DM without MCI (termed T2DM-nMCI) or with MCI (termed T2DM-MCI). There were no significant differences for sex, T2DM years, hypertension, hyperlipidemia, coronary disease, complications, insulin treatment, HbA1c, ApoE ε2, ApoE ε3, tGSK3β and pS9GSK3β between the two groups. Compared with the T2DM-nMCI group, T2DM-MCI group showed lower MMSE score with older age, ApoE ε4 allele, higher olfactory score and higher rGSK-3β (ratio of total GSK-3β to Ser9-phosphorylated GSK-3β) in the training set and the validation set. The OR values of age, ApoE ε4 gene, olfactory score and rGSK-3β were 1.09, 2.09, 1.51, 10.08 in the training set, and 1.06, 2.67, 1.47, 7.19 in the validation set, respectively. The diagnostic accuracy of age, ApoE ε4 gene, olfactory score and rGSK-3β were 0.76, 0.72, 0.66, 0.79 in the training set, and 0.70, 0.68, 0.73, 0.79 in the validation set, respectively. These four combined biomarkers had the area under the curve (AUC) of 82% and 86%, diagnostic accuracy of 83% and 81% in the training set and the validation set, respectively.InterpretationAging, activation of peripheral circulating GSK-3β, expression of ApoE ε4 and increase of olfactory score are diagnostic for the mild cognitive impairment in T2DM patients, and combination of these biomarkers can improve the diagnostic accuracy