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Background Leaves, flowers and young shoots of yellow Camellia species are often used as a substitute for green tea in Vietnam. Yellow Camellia species contain high levels of polyphenol compounds, and have shown activities such as antioxidant, anticancer, and cytotoxic. Objectives We qualitatively screened phytochemicals, quantified total polyphenols of 70% ethanol (EtOH) extracts of leaves, young shoots, and flowers of Camellia vuquangensis and Camellia hatinhensis in Ha Tinh Province, Vietnam. Furthermore, these extracts have been evaluated for lipid peroxidation inhibitory activities at the in vivo level in the BALB/c mouse model, and in vitro cytotoxic activities. Materials and Methods Chemical methods and thin-layer chromatographic (TLC) analysis were used for the qualitative screening of phytochemicals. High-performance liquid chromatography (HPLC) was used to determine total polyphenols. Cell survival was determined through optical density (OD) measured when the protein composition of the cells was stained with sulforhodamine B (SRB). Inhibition of lipid peroxidation was evaluated by determining the content of malondialdehyde (MDA), which is a product of membrane lipid peroxidation. Results The total polyphenol contents of all parts of the two species were comparable to that of green tea with values between 319.3 and 342.6 mg gallic acid equivalents (GAE/g) dry weight. Extracts of leaves, flowers of C. vuquangensis and C. hatinhensis showed strong lipid peroxidation inhibitory activities (IC50: 7.92–17.45 µg/mL) and moderate cytotoxic activities against cell lines HepG2, A549, MCF7, SK-Mel-2, HT-29, and AGS (IC50: 34.73–80.58 µg/mL). Conclusion These two tea species may be considered as herbal teas with various health benefits.

Myoporum sandwicense A. Gray (naio) is one of the characteristic trees of Hawaiian montane–subalpine mesic forests. In this study, lab-distilled oils of M. sandwicense leaves, wood, and twigs growing on the island of Hawaii, as well as industrially produced wood oils, were characterized by gas chromatography–mass spectrometry (GC-MS). The lab-distilled oils were screened for antimicrobial activity. M. sandwicense leaf essential oil was rich in β-caryophyllene (15.1%), α-humulene (12.8%), germacrene D (7.9%), bicyclogermacrene (12.5%), brigalow ketol (9.6%), and myoporone (16.8%), while the wood essential oils were dominated by α-bisabolol and trans-α-bisabolol oxide B. The sapwood oil was dominated by palmitic acid (35.5%), linoleic acid (19.7%), oleic acid (31.9%), and stearic acid (5.7%), whereas the oil from twigs was rich in tricosane (77.3%) and pentacosane (13.1%). M. sandwicense essential oils were screened for antimicrobial activity against a panel of potentially pathogenic bacteria and fungi. The leaf essential oil of M. sandwicense showed excellent antibacterial activity against S. pyogenes and antifungal activity against A. fumigatus. The wood essential oil showed notable activity against S. pyogenes, A. fumigatus,A. niger, and M. gypseum. The twig oil was remarkably active against mold species. This work is the first report we are aware of on the composition and antimicrobial properties of naio essential oils.

The 2017 detection of a kilonova coincident with gravitational-wave emission has identified neutron star mergers as the major source of the heaviest elements, and dramatically constrained alternative theories of gravity. Observing a population of such sources has the potential to transform cosmology, nuclear physics, and astrophysics. However, with only one confident multi-messenger detection currently available, modelling the diversity of signals expected from such a population requires improved theoretical understanding. In particular, models which are quick to evaluate, and are calibrated with more detailed multi-physics simulations, are needed to design observational strategies for kilonovae detection, and to obtain rapid-response interpretations of new observations. We use grey-opacity models to construct populations of kilonovae, spanning ejecta parameters predicted by numerical simulations. Our modelling focuses on wavelengths relevant for upcoming optical surveys, such as the Rubin Observatory Legacy Survey of Space and Time (LSST). In these simulations, we implement heating rates that are based on nuclear reaction network calculations. We create a Gaussian-process emulator for kilonova grey opacities, calibrated with detailed radiative transfer simulations. Using recent fits to numerical relativity simulations, we predict how the ejecta parameters from BNS mergers shape the population of kilonovae, accounting for the viewing-angle dependence. Our simulated population of binary neutron star (BNS) mergers produce peak i-band absolute magnitudes $-20 \leq M_i \leq -11$. A comparison with detailed radiative transfer calculations indicates that further improvements are needed to accurately reproduce spectral shapes over the full light curve evolution., 14 pages, 12 figures, 2 tables, matches version accepted to MNRAS. Fixes a software bug from previous versions which incorrectly determined the kilonovae ejecta velocities, v4: added link to public code package https://github.com/cnsetzer/kilopop

BACKGROUND: Prospective genetic evaluation of patients at our referral research hospital presents clinical research challenges. OBJECTIVE: This study sought not only a single-gene explanation for participants’ immune-related presentations, but viewed each participant holistically, with the potential to have multiple genetic contributions to their immune-phenotype and other heritable comorbidities relevant to their presentation and health. METHODS: We developed a program integrating exome sequencing, chromosomal microarray, phenotyping, results return with genetic counseling, and reanalysis in 1505 individuals from 1000 families with suspected or known inborn errors of immunity. RESULTS: Probands were 50.8% female, 71.5% ≥18 years, and had diverse immune presentations. Overall, 327/1000 probands (32.7%) received 361 molecular diagnoses. These included 17 probands with diagnostic copy number variants, 32 probands with secondary findings, and 31 probands with multiple molecular diagnoses. Reanalysis added 22 molecular diagnoses, predominantly due to new disease-gene associations (9/22, 40.9%). One-quarter of the molecular diagnoses (92/361) did not involve immune-associated genes. Molecular diagnosis was correlated with younger age, male sex, and a higher number of organ systems involved. This program also facilitated the discovery of new gene-disease associations such as SASH3-related immunodeficiency. A review of treatment options and ClinGen actionability curations suggest that at least 251/361 (69.5%) of these molecular diagnoses could translate into ≥1 management option. CONCLUSION: This program contributes to our understanding of the diagnostic and clinical utility whole exome analysis on a large scale.

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by chronic nonmalignant lymphadenopathy, splenomegaly, cytopenias, and other autoimmune manifestations. ALPS is caused by lymphocyte accumulation from defects in FAS-mediated apoptosis. Heterozygous germline or somatic pathogenic single nucleotide variants in FAS are the most common molecular etiology of ALPS. Through the Centralized Sequencing Program at the National Institute of Allergy and Infectious Diseases, we performed exome sequencing on subjects with a clinical diagnosis of ALPS, with a subset receiving copy number variant (CNV) analysis. In this cohort, we identified 3 subjects from unrelated families with CNVs at the FAS locus. One subject had a de novo ∼0.828 Mb copy number loss encompassing all of FAS. The second subject had a maternally inherited ∼1.004 Mb copy number loss encompassing all of FAS. The third subject had a paternally inherited ∼0.044 Mb copy number loss encompassing exons 7 through 9 of FAS. Subjects with deletions in FAS had clinical presentations and biomarker profiles similar to those with ALPS and with germline and somatic FAS variants. We demonstrate that CNV analysis should be pursued if there is clinical and biomarker evidence of ALPS because it can lead to a molecular diagnosis and appropriate treatment when FAS sequencing is inconclusive.

Endodontic surgery encompasses several procedures for the treatment of teeth with a history of failed root canal treatment, such as root-end surgery, crown and root resections, surgical perforation repair and intentional replantation. Endodontic microsurgery is the evolution of the traditional apicoectomy techniques and incorporates high magnification, ultrasonic root-end preparation and root-end filling with biocompatible filling materials. Modern endodontic surgery uses the dental operating microscope, incorporates cone-beam computed tomography (CBCT) for preoperative diagnosis and treatment planning, and has adopted piezoelectric approaches to osteotomy and root manipulation. Crown and root resection techniques have benefitted from the same technological advances. This review focuses on the current state of root-end surgery by comparing the techniques and materials applied during endodontic microsurgery to the most widely used earlier methods and materials. The most recent additions to the clinical protocol and technical improvements are discussed, and an outlook on future directions is given. Whilst nonsurgical retreatment remains the first choice to address most cases with a history of endodontic failure, modern endodontic microsurgery has become a predictable and minimally invasive alternative for the retention of natural teeth.

Prosopis is a regional cash crop that is widely grown in arid, semiarid, tropical, and subtropical areas. Compared with other legume plants, Prosopis is underutilized and has great potentialities. Prosopis not only is a good source of timber, construction, fencing material, and gum, but also can be applied for food, beverage, feed, and medicine. Prosopis contains numerous phytochemical constituents, including carbohydrates, proteins, fatty acids, minerals, and vitamins, while varieties of phenolic compounds have also been identified from different parts of Prosopis. Flavonoids (especially C-glycosyl flavonoids), tannins, catechin, 4′-O-methyl-gallocatechin, mesquitol, and quercetin O-glycosides are significant phenolic contents in Prosopis. Various extracts of Prosopis displayed a wide range of biological properties, such as antioxidant, antihyperglycemic, antibacterial, anthelmintic, antitumor, and anticancer. Additionally, Prosopis has the potential to be an ideal diet that contains abundant dietary fiber, minerals, galactomannans, and low-fat content. However, the bioactivity and pharmacological properties associated with Prosopis were influenced by the bioavailability of phytochemicals, various antinutritional compounds, and the interactions of protein and phenolic compounds. The bioavailability of Prosopis is mainly affected by phenolic contents, especially catechin. The antinutritional compounds negatively affect the nutritional qualities of Prosopis, which can be prevented by heating. The protein-phenolic compound interactions can help the human body to absorb quercetin from Prosopis. This literature review aimed to provide systematic information on the physical, biochemical, pharmacological, and nutritional properties and potential applications of Prosopis.

Single-center series.Intraspinal facet joint cysts can lead to nerve root compression symptoms with severe discomfort and disability. Permanent improvement can be achieved by surgical resection of the cyst. However, cerebrospinal fluid (CSF) leakage is a common problem in resection of facet joint cyst.The aim of the study was to investigate the frequency of CSF leak after resection of a joint cyst and to determine predictive factors.A total of 176 consecutive patients underwent surgery for lumbar spinal facet joint cyst in our institution between 1997 and 2018. Patients with a CSF leak were compared with patients without a CSF leak (control group).CSF leakage occurred in 14 patients (8.0%) In 2 of the cases (14.3%), the CSF leak was recognized only postoperatively, in 12 cases (85.7%), the CSF leak was detected intraoperatively. Despite intraoperative dura repair, 4 of these 12 patients (33.3%) presented with CSF leakage postoperatively. Altogether 6 patients had postoperative CSF leakage. Compared with patients without CSF leak, there were no differences in preoperative symptoms, surgical technique, complications, or postoperative findings. Adhesion of the cyst to the dura mater was present in all 14 patients with CSF leakage (100%), but only 61.7% of the control group ( P0.005). All patients in the CSF leak group showed an improvement of their preoperative symptoms.The rate of CSF leakage in resection of spinal facet joint cyst was 8% in the present study. The occurrence of a CSF leakage was independent of clinical factors, level, or side of the cyst, but significantly correlated to dural adhesion of the cyst.Since neither clinical recovery nor recurrence rates do depend on complete removal of the cyst, aggressive resection of dural adherend parts of the cyst wall should be avoided to prevent CSF leakage.

The Amazon is the largest rainforest on the planet and was an important carbon sink. The carbon sink is declining, mainly due to an increase in tree mortality as a result of deforestation, degradation, and local, regional and global climate change. In addition, deforestation and forest degradation reduce the ability of the Amazon rainforest to act as a carbon sink. CO2 Vertical Profiles (VP) were performed from 2010 to 2021 (805), using small aircraft at 4 locations: SAN (2.86° S 54.95° W), ALF (8.80° S 56.75° W), RBA (9.38° S 67.62° W) and from 2010 to 2012 on TAB (5.96° S 70.06° W) and since 2013 at TEF (3.39° S 65.55° W). The question if Amazonia is a carbon source or sink is an important role in the global carbon budget. Amazonia vertical profile annual mean derived from CO2 annual mean vertical profiles (VP subtracted from the background concentration: ∆VP) from the 4 studied sites can help to clarify this important question. The sampling frequency was approximately 2 times per month in each location, from 4.4 km height (a.s.l.) until near surface 300 m (a.s.l.), and usually carried out between 12:00 and 13:00 local time. The CO2 samples were analyzed at INPE's LaGEE (Greenhouse Gas Laboratory), in São Jose dos Campos. This result is a direct indication of the regional source in the global carbon budget, indeed there are well-known discrepancies from many studies using different methodologies (bottom-up, top-down techniques, and a wide variety of global, regional, and inversion models). In this study, we will present Carbon flux from the time series for the 4 sites and Amazon Carbon balance using the column budget technique, and analyze the correlations with various parameters related to climate, vegetation, deforestation, and biomass burning.

This paper addresses the long-standing question of the predicativity of the Mahlo universe. A solution, called the extended predicative Mahlo universe, has been proposed by Kahle and Setzer in the context of explicit mathematics. It makes use of the collection of untyped terms (denoting partial functions) which are directly available in explicit mathematics but not in Martin-Löf type theory. In this paper, we overcome the obstacle of not having direct access to untyped terms in Martin-Löf type theory by formalizing explicit mathematics with an extended predicative Mahlo universe in Martin-Löf type theory with certain indexed inductive-recursive definitions. In this way, we can relate the predicativity question to the fundamental semantics of Martin-Löf type theory in terms of computation to canonical form. As a result, we get the first extended predicative definition of a Mahlo universe in Martin-Löf type theory. To this end, we first define an external variant of Kahle and Setzer’s internal extended predicative universe in explicit mathematics. This is then formalized in Martin-Löf type theory, where it becomes an internal extended predicative Mahlo universe. Although we make use of indexed inductive-recursive definitions that go beyond the type theory $\mathbf {IIRD}$ of indexed inductive-recursive definitions defined in previous work by the authors, we argue that they are constructive and predicative in Martin-Löf’s sense. The model construction has been type-checked in the proof assistant Agda.

Morusin is a natural product that has been isolated from the bark of Morus alba, a species of mulberry tree. It belongs to the flavonoid family of chemicals, which is abundantly present in the plant world and is recognized for its wide range of biological activities. Morusin has a number of biological characteristics, including anti-inflammatory, anti-microbial, neuro-protective, and antioxidant capabilities. Morusin has exhibited anti-tumor properties in many different forms of cancer, including breast, prostate, gastric, hepatocarcinoma, glioblastoma, and pancreatic cancer. Potential of morusin as an alternative treatment method for resistant malignancies needs to be explored in animal models in order to move toward clinical trials. In the recent years several novel findings regarding the therapeutic potential of morusin have been made. This aim of this review is to provide an overview of the present understanding of morusin’s beneficial effects on human health as well as provide a comprehensive and up-to-date discussion of morusin’s anti-cancer properties with a special focus on in vitro and in vivo studies. This review will aid future research on the creation of polyphenolic medicines in the prenylflavone family, for the management and treatment of cancers.

PurposeThough copy number variants (CNVs) have been suggested to play a significant role in inborn errors of immunity (IEI), the precise nature of this role remains largely unexplored. We sought to determine the diagnostic contribution of CNVs using genome-wide chromosomal microarray analysis (CMA) in children with IEI.MethodsWe performed exome sequencing (ES) and CMA for 332 unrelated pediatric probands referred for evaluation of IEI. The analysis included primary, secondary, and incidental findings.ResultsOf the 332 probands, 134 (40.4%) received molecular diagnoses. Of these, 116/134 (86.6%) were diagnosed by ES alone. An additional 15/134 (11.2%) were diagnosed by CMA alone, including two likely de novo changes. Three (2.2%) participants had diagnostic molecular findings from both ES and CMA, including two compound heterozygotes and one participant with two distinct diagnoses. Half of the participants with CMA contribution to diagnosis had CNVs in at least one non-immune gene, highlighting the clinical complexity of these cases. Overall, CMA contributed to 18/134 diagnoses (13.4%), increasing the overall diagnostic yield by 15.5% beyond ES alone.ConclusionPairing ES and CMA can provide a comprehensive evaluation to clarify the complex factors that contribute to both immune and non-immune phenotypes. Such a combined approach to genetic testing helps untangle complex phenotypes, not only by clarifying the differential diagnosis, but in some cases by identifying multiple diagnoses contributing to the overall clinical presentation.

Spinal tuberculosis is due to globalization no longer a disease limited to developing nations. It remains in Germany a rarity and still a difficult diagnosis. Here we analyzed patients with spinal tuberculosis treated at our neurosurgical department. According to the infected anatomic segment, patients were assigned in one of three groups. Surgery was performed when neurological deficit due to mechanical compression, deformity, instability, severe pain, necrotic bone or failure to respond to anti-tuberculous treatment were observed. We identified 34 patients with spinal tuberculosis who underwent surgical treatment. In the cervical spinal tuberculosis group, there were 15 cases (46.9%) In most cases treatment consisted of spinal instrumentation. In the thoracic group, 10 cases (29.4%) were observed. The treatment was performed by dorsolateral spinal instrumentation. For the thoracolumbar group, 9 cases (26.4%) were observed. In most cases dorsolateral spinal instrumentation was performed. One patient in the first group and one patient in the third group relapsed after operation. A second surgery was necessary. Patients with chronic back pain, immigration background and/or neurological deficit spinal TB should be considered as a differential diagnosis. Combined surgical intervention and medical treatment is associated with a favorable outcome.

Outpatient parenteral antimicrobial therapy (OPAT) is a cost-effective method of administering intravenous antimicrobial therapy. Although OPAT is well established in the UK and US healthcare systems, few centres in Europe perform it. Here we analysed OPAT for the treatment of patients with spinal infections at our institution. In this retrospective study, patients with spinal infection who required intravenous (i.v.) antimicrobial treatment between 2018 and 2021 were analysed. The duration of short-term antimicrobial treatment for skin and soft tissue infections and complex infections requiring long-term antimicrobial treatment, such as spinal bone or joint infections, were analysed. All patients were discharged with a peripherally inserted central catheter (PICC) line. Prior to discharge, all patients received training in the safe administration of their medications via the PICC line. The duration of OPAT and the rate of readmission after OPAT were analysed. For this study a total of 52 patients who were treated via OPAT due to spinal infections were analyzed. In 35 cases (69.2%) complex spinal infection was reason for i.v. antimicrobial therapy. Surgery was required in 23 of these 35 patients (65.7%). The average hospital stay for these patients was 12 ± 6 days. The remaining 17 patients were treated for an infection of the soft tissue or the skin and hospital stay for these patients was on average 8 ± 4 days. Gram-positive organisms were isolated in 64.4%. Staphylococcus aureus followed by other Staphylococcus species, was the most common detected organism. After discharging i.v. antimicrobial treatment was given for an average of 20 ± 14 days. The duration of antimicrobial treatment for soft tissue was 10.8 ± 8 days, and for complex infections 25.1 ± 18 days. The mean follow-up was 21 ± 14 months. There was one case of readmission due to treatment failure. There were no difficulties encountered in implementing OPAT. OPAT is a feasible and effective option for delivering intravenous antimicrobial therapy to patients with spinal infections who can be managed without hospitalisation. OPAT offers patient-centred treatment at home while avoiding the risks associated with hospitalisation, with high levels of patient satisfaction.

Phytates are a type of organophosphorus compound produced in terrestrial ecosystems by plants. In plant feeds, phytic acid and its salt form, phytate, account for 60%–80% of total phosphorus. Because phytate is a polyanionic molecule, it can chelate positively charged cations such as calcium, iron, and zinc. Due to its prevalence in vegetal tissues and the fact that people consume plants, phytate was first considered a potential health benefit. This updated review aims to summarize the current data on the results of clinical trials of phytates on human health, highlighting both beneficial and undesirable effects. To obtain these updated data, published papers in electronic databases such as PubMed/MedLine, TRIP database, Wiley, Google Scholar, Baidu, and Scopus were searched. Study results have shown that phytate can have beneficial health effects such as antioxidant, anticancer potential and reduction of pathological calcifications in blood vessels and organs; but also, negative effects by reducing the absorption of minerals important for maintaining the homeostasis of the human body. According to these recent results derived from recent clinical studies, phytates may be a potential natural source for health benefits. To improve clinical efficacy and human health benefits, further dose-response studies are needed to determine effective therapeutic doses and potential interactions with conventional drugs.

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Rampant activity of the hypoxia-inducible factor (HIF)-1 in cancer is frequently associated with the malignant progression into a harder-to-treat, increasingly aggressive phenotype. Clearly, anti-HIF strategies in cancer cells are of considerable clinical interest. One way to fine-tune, or inhibit, HIF's transcriptional outflow independently of hydroxylase activities could be through competing transcription factors. A CACGTG-binding activity in human hepatoma cells was previously found to restrict HIF's access to hypoxia response cis-elements (HRE) in a Daphnia globin gene promoter construct (phb2). The CACGTG factor, and its impact on hypoxia-responsive human genes, was analyzed in this study by genome-wide computational scans as well as gene-specific quantitative PCR, reporter and DNA-binding assays in hepatoma (Hep3B), cervical carcinoma (HeLa), and breast carcinoma (MCF7) cells. Among six basic helix-loop-helix transcription factors known to target CACGTG palindromes, we identified upstream stimulatory factor (USF)-1/2 as predominant phb2 CACGTG constituents in Hep3B, HeLa, and MCF7 cells. Human genes with adjacent or overlapping HRE and CACGTG motifs included with lactate dehydrogenase A (LDHA) and Bcl-2/E1B 19 kDa interacting protein 3 (BNIP3) hypoxia-induced HIF-1 targets. Parallel recruitment of HIF-1α and USF1/2a to the respective promoter chromatin was verified for all cell lines investigated. Mutual complementing (LDHA) or moderating (BNIP3) cross-talk was seen upon overexpression or silencing of HIF-1α and USF1/2a. Distinct (LDHA) or overlapping (BNIP3) promoter-binding sites for HIF-1 and USFs were subsequently characterized. We propose that, depending on abundance or activity of its protein constituents, O2-independent USF signaling can function to fine-tune or interfere with HIF-mediated transcription in cancer cells. Mol Cancer Res; 9(11); 1520–36. ©2011 AACR.

Knema is one of the genera in the Myristicaceae family. The genus includes 60 species in Southeast Asia and is traditionally used for treating skin disorders. Here, for the first time, the essential oil, anti-tyrosinase, and molecular docking studies of Knema intermedia were evaluated. The essential oil was obtained by hydrodistillation and fully characterized by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Anti-tyrosinase activity was evaluated against mushroom tyrosinase, whereas molecular docking studies were performed using Autodock vina embedded in PyRx to evaluate the binding interactions of major components. A total of 37 components (97.3%) were successfully identified in the essential oil, which was characterized by high amounts of t-muurolol (20.1%), α-copaene (14.4%), δ-cadinene (13.9%), germacrene B (9.5%), and δ-selinene (7.0%). The essential oil displayed moderate inhibitory activity towards tyrosinase with an IC50 value of 70.2 μg/mL. The best docking energy was observed with δ-selinene (−7.8 kcal/mol), and it also forms interactions with His85, His263, and His244 which are important amino acid residues of the tyrosinase receptor. Hence, this study provides valuable scientific data on K. intermedia as potential candidate for the development of natural antiaging formulations.

Crocus species are mainly distributed in North Africa, Southern and Central Europe, and Western Asia, used in gardens and parks as ornamental plants, while Crocus sativus L. (saffron) is the only species that is cultivated for edible purpose. The use of saffron is very ancient; besides the use as a spice, saffron has long been known also for its medical and coloring qualities. Due to its distinctive flavor and color, it is used as a spice, which imparts food preservative activity owing to its antimicrobial and antioxidant activity. This updated review discusses the biological properties of Crocus sativus L. and its phytoconstituents, their pharmacological activities, signaling pathways, and molecular targets, therefore highlighting it as a potential herbal medicine. Clinical studies regarding its pharmacologic potential in clinical therapeutics and toxicity studies were also reviewed. For this updated review, a search was performed in the PubMed, Science, and Google Scholar databases using keywords related to Crocus sativus L. and the biological properties of its phytoconstituents. From this search, only the relevant works were selected. The phytochemistry of the most important bioactive compounds in Crocus sativus L. such as crocin, crocetin, picrocrocin, and safranal and also dozens of other compounds was studied and identified by various physicochemical methods. Isolated compounds and various extracts have proven their pharmacological efficacy at the molecular level and signaling pathways both in vitro and in vivo. In addition, toxicity studies and clinical trials were analyzed. The research results highlighted the various pharmacological potentials such as antimicrobial, antioxidant, cytotoxic, cardioprotective, neuroprotective, antidepressant, hypolipidemic, and antihyperglycemic properties and protector of retinal lesions. Due to its antioxidant and antimicrobial properties, saffron has proven effective as a natural food preservative. Starting from the traditional uses for the treatment of several diseases, the bioactive compounds of Crocus sativus L. have proven their effectiveness in modern pharmacological research. However, pharmacological studies are needed in the future to identify new mechanisms of action, pharmacokinetic studies, new pharmaceutical formulations for target transport, and possible interaction with allopathic drugs.

To prospect an isozyme-specific, effective inhibitor against the physiologically-crucial enzyme phosphodiesterase 1 (PDE1), phytochemicals from Pistacia integerrima galls were screened. The chloroform fraction of gall extract was subjected to column chromatographic which led to the isolation of compound 1, elucidated to be 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one (a flavone). In vitro and in silico PDE1 inhibitory activity of the compound 1 was investigated. EDTA, a known PDE1 inhibitor, was used as the reference. The flavone exhibited in vitro attenuation towards snake venom PDE1. IC50 response was superior to the standard chelator. An in silico molecular docking study was carried out using 3D structure of PDE1 to study the binding interactions of compound 1. The docking study predicted that flavone had a lower binding affinity (-7.6 kcal/mol) and total energy (-95 kcal/mol) score compared to EDTA. The minimal energy associated with the ligand-protein complex implied that isolated compound 1 can serve as a therapeutic agent against PDE1 enzyme-provoked ailments like asthma, hypertension, schizophrenia, and erectile dysfunction.

Objective To explore potential natural products against severe acute respiratory syndrome coronavirus (SARS-CoV-2) via the study of structural and non-structural proteins of human coronaviruses. Methods In this study, we performed an in-silico survey of 25 potential natural compounds acting against SARS-CoV-2. Molecular docking studies were carried out using compounds against 3-chymotrypsin-like protease (3CLPRO), papain-like protease (PLPRO), RNA-dependent RNA polymerase (RdRp), non-structural protein (nsp), human angiotensin converting enzyme 2 receptor (hACE2R), spike glycoprotein (S protein), abelson murine leukemia viral oncogene homolog 1 (ABL1), calcineurin-nuclear factor of activated T-cells (NFAT) and transmembrane protease serine 2. Results Among the screened compounds, amentoflavone showed the best binding affinity with the 3CLPRO, RdRp, nsp13, nsp15, hACE2R. ABL1 and calcineurin-NFAT; berbamine with hACE2R and ABL1; cepharanthine with nsp10, nsp14, nsp16, S protein and ABL1; glucogallin with nsp15; and papyriflavonol A with PLPRO protein. Other good interacting compounds were juglanin, betulinic acid, betulonic acid, broussooflavan A, tomentin A, B and E, 7-methoxycryptopleurine, aloe emodin, quercetin, tanshinone I, tylophorine and furruginol, which also showed excellent binding affinity towards a number of target proteins. Most of these compounds showed better binding affinities towards the target proteins than the standard drugs used in this study. Conclusion Natural products or their derivatives may be one of the potential targets to fight against SARS-CoV-2. Electronic Supplementary Material Supplementary materials (Appendixes 1–6) are available in the online version of this article at DOI: 10.1007/s11655-021-3504-5

Introduction The identification of C-shaped root canal anatomy on radiographic images affects clinical decision making and treatment. The aims of this study were to develop a deep learning (DL) model to classify C-shaped canal anatomy in mandibular second molars from cone-beam computed tomographic (CBCT) volumes and to compare the performance of 3 different architectures. Methods U-Net, residual U-Net, and Xception U-Net architectures were used for image segmentation and classification of C-shaped anatomies. Model training and validation were performed on 100 of a total of 135 available limited field of view CBCT images containing mandibular molars with C-shaped anatomy. Thirty-five CBCT images were used for testing. Voxel-matching accuracy of the automated labeling of the C-shaped anatomy was assessed with the Dice index. The mean sensitivity of predicting the correct C-shape subcategory was calculated based on detection accuracy. One-way analysis of variance and post hoc Tukey honestly significant difference tests were used for statistical evaluation. Results The mean Dice coefficients were 0.768 ± 0.0349 for Xception U-Net, 0.736 ± 0.0297 for residual U-Net, and 0.660 ± 0.0354 for U-Net on the test data set. The performance of the 3 models was significantly different overall (analysis of variance, P = .000779). Both Xception U-Net (Q = 7.23, P = .00070) and residual U-Net (Q = 5.09, P = .00951) performed significantly better than U-Net (post hoc Tukey honestly significant difference test). The mean sensitivity values were 0.786 ± 0.0378 for Xception U-Net, 0.746 ± 0.0391 for residual U-Net, and 0.720 ± 0.0495 for U-Net. The mean positive predictive values were 77.6% ± 0.1998% for U-Net, 78.2% ± 0.0.1971% for residual U-Net, and 80.0% ± 0.1098% for Xception U-Net. The addition of contrast-limited adaptive histogram equalization had improved overall architecture efficacy by a mean of 4.6% (P Conclusions DL may aid in the detection and classification of C-shaped canal anatomy.

Abstract: Xanthones are widely distributed polyphenols, present commonly in higher plants; Garcinia, Calophyllum, Hypericum, Platonia, Mangifera, Gentiana and Swertia. Xanthone tricyclic scaffold is able to interact with different biological targets, showing antibacterial and cytotoxic effects, as well as potent effects against osteoarthritis, malaria, and cardiovascular diseases. Thus, in this article we focused on pharmacological effects, applications and preclinical studies with the recent updates of xanthon´s isolated compounds from 2017-2020. We found that only α-mangostin, gambogic acid, and mangiferin, have been subjected to preclinical studies with particular emphasis on the development of anticancer, diabetes, antimicrobial and hepatoprotective therapeutics. Molecular docking calculations were performed to predict the binding affinities of xanthone-derived compounds against SARS-CoV-2 Mpro. According to the results, cratoxanthone E and morellic acid demonstrated promising binding affinities towards SARS-CoV-2 Mpro with docking scores of −11.2 and −11.0 kcal/mol, respectively. Binding features manifested the capability of cratoxanthone E and morellic acid to exhibit nine and five hydrogen bonds, respectively, with the key amino acids of the Mpro active site. In conclusion, cratoxanthone E and morellic acid are promising anti-COVID-19 drug candidates that warrant further detailed in vivo experimental estimation and clinical assessment.

Background The incidence of pyogenic spinal infection has increased in recent years. In addition to treating the spinal infection, optimal care also includes identifying the source of the pyogenic spinal infection and the presence of other infections. The aim of this study is to elucidate the prevalence of oral cavity infection (OCI) within this Patients cohort. Methods As part of a prospective study conducted from 2016 to 2021, the number of patients with dental infections was investigated by means of an orthopantomogram (OPG) and subsequent dental examination. Results The presence of an oral infection was investigated in 55 (47%) of 118 patients by an OPG, 29 (53%) of whom had a corresponding abnormality of the oral cavity. In addition to the spinal infection, patients with an oral cavity infection revealed an increased incidence of endocarditis, sepsis and brain abscess. A spinal epidural abscess, a multilevel affection of the infection and an elevated CRP value were also found in patients with a co-existing oral cavity infection. Back pain assessed at admission and 3 months after surgery was also more pronounced in patients with an oral cavity infection. Neurological deficits were often present in patients with spinal and oral cavity infection. Conclusions The presence of an oral cavity infection proves to be one of the important factors in the detection of the source of the pyogenic spinal infection. In addition, a pronounced spinal affection and frequent co-infections were seen in patients with an oral cavity infection.

Objective Spinal tuberculosis, known as Pott´s disease, is a rare but serious clinical condition which can lead to severe deformity and neurological complications. The majority of cases occur in population-dense developing countries like Africa or India, but due to globalization it is no longer a disease limited to developing nations. Thus it should be considered in patients with persistent back pain, who are at high risk, such as migrant population and immunocompromised patients. Nevertheless spinal tuberculosis remains in Germany a rarity and still a difficult diagnosis. Here we analyzed patients with Pott´s disease treated at our neurosurgical department supplying medical care for a mideuropean metropolitan region. Methods Patients with cervical, thoracic and thoracolumbar spinal tuberculosis between 2014 and 2022 were retrospectively analyzed. According to the infected anatomic segment, patients were assigned in one of three groups. All patients were evaluated clinically using the visual analog scale (VAS). American Spinal Injury Association (ASIA) impairment scale was used for assessment of neurological status. Surgery was performed when neurological deficit due to mechanical compression, deformity, instability, severe pain, necrotic bone or failure to respond to anti-tuberculous treatment were observed. Long term follow-up as well as complications related to surgery were recorded and analyzed. Results We identified 34 patients with spinal tuberculosis who underwent surgical treatment. All included patients had an immigrat background. In the cervical spinal tuberculosis group, there were 15 cases (46.9 %) with a mean age of 31.6+/-12 years. In 13 cases (86.7%) treatment consisted of spinal instrumentation. For two patient surgical debridement of the infected vertebrae and disc material and fusion was performed. In the thoracic spinal tuberculosis group, there were 10 cases (29.4%) with a mean age of 37.7+/-16 years. The treatment was performed by dorsolateral spinal instrumentation. In the thoracolumbar spinal tuberculosis group, there were 9 cases (26.4%) with a mean age of 44.1 +/-21 years. In five cases dorsolateral spinal instrumentation and in three cases only dorsal instrumentation was performed. The mean follow-up time was 47 months (range 6-96 months). All included patients demonstrated clinical healing of tuberculosis infection. Bony fusion was achieved in 94.1 % with no loosening or breakage of internal fixation. In all three groups, the VAS pain score at 8 weeks after operation and at the most recent follow-up were lower than the preoperative level. One patient in the first group and one patient in the third group relapsed after operation. A second surgery was necessary. In eight cases (23.5%) neurological impairment (ASIA D) and in one case (2.9%) ASIA C was described, which regressed completely (ASIA E). Conclusion Our results highlight the role of early surgery in the management of spinal tuberculosis. Patients with chronic back pain, immigration background and/or neurological deficit spinal TB should be considered as a differential diagnosis. Aggressive diagnosis of spinal TB is necessary and combined surgical intervention and medical treatment is associated with a favorable outcome.

This article examines the local outcomes of São Paulo city’s engagement in transnational networks for climate protection. The participation of municipalities in such networks has been an important driver in fostering local initiatives to protect global climate. There have been accounts of many cases of mitigation measures implemented successfully at the local level, demonstrating significant carbon emissions reductions, thus helping national governments in their emissions reductions efforts. However, few studies have explored the linkages between transnational engagement, implementation of subnational climate action, and the actual national commitments in developing countries. This paper assesses the role of local engagement in transnational networks in the adoption and implementation of climate policies and legislation in the city of São Paulo, and its impact on the Brazilian government’s climate action, in the period between 2002 and 2014. São Paulo was an active member of ICLEI’s Cities for Climate Protection campaign and the C40 network during this period. The city was the first government to adopt legislation establishing reduction targets in 2009. However, while transnational action influenced the inception of the city’s climate change policy, it has had limited impact on the implementation of climate action beyond the municipal level. The role of transnational action, in this context, is yet to be determined.

Supplemental material, sj-docx-1-npx-10.1177_1934578X231154965 for Chemical Characterization of Three Artemisia tridentata Essential Oils and Multivariate Analyses: A Preliminary Investigation by Kathy Swor, Prabodh Satyal, Ambika Poudel and William N Setzer in Natural Product Communications

Supplemental material, sj-docx-1-npx-10.1177_1934578X231187699 for The Essential Oil Composition of Anthriscus caucalis M. Bieb. (Apiaceae) Growing Wild in Southwestern Idaho by Kathy Swor, Prabodh Satyal and William N Setzer in Natural Product Communications

Supplemental material, sj-docx-2-npx-10.1177_1934578X231154965 for Chemical Characterization of Three Artemisia tridentata Essential Oils and Multivariate Analyses: A Preliminary Investigation by Kathy Swor, Prabodh Satyal, Ambika Poudel and William N Setzer in Natural Product Communications

Supplemental material, sj-docx-1-npx-10.1177_1934578X231187699 for The Essential Oil Composition of Anthriscus caucalis M. Bieb. (Apiaceae) Growing Wild in Southwestern Idaho by Kathy Swor, Prabodh Satyal and William N Setzer in Natural Product Communications

Presentation to SOT in Nashville TN on March 19-23, 2023 Science Inventory, CCTE products: https://cfpub.epa.gov/si/si_public_search_results.cfm?advSearch=true&showCriteria=2&keyword=CCTE&TIMSType=&TIMSSubTypeID=&epaNumber=&ombCat=Any&dateBeginPublishedPresented=07/01/2017&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&DEID=&personName=&personID=&role=Any&journalName=&journalID=&publisherName=&publisherID=&sortBy=pubDate&count=25