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Nupur U Patel,1 Catherine Roach,1 Hossein Alinia,1 William W Huang,1 Steven R Feldman1–3 1Department of Dermatology, Center for Dermatology Research, Wake Forest University School of Medicine, Winston-Salem, NC, 2Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, 3Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA Abstract: Acanthosis nigricans (AN) is a common dermatologic manifestation of systemic disease that is associated with insulin resistance, diabetes mellitus, obesity, internal malignancy, endocrine disorders, and drug reactions. Treatment of AN primarily focuses on resolution of the underlying disease processes causing the velvety, hyperpigmented, hyperkeratotic plaques found on the skin. While the goal of therapy is to treat the primary cause, cosmetic resolution of AN lesions can be important for patients and their quality of life. Treatment options for AN have not been extensively studied; however, smaller powered clinical trials and case reports exist in the literature. Our review aims to explore and evaluate the current treatment options that exist for AN. Keywords: acanthosis nigricans, diabetes, obesity, hyperinsulinemia, dermatologic condition, dermatology, malignant acanthosis, pseudoacanthosis, metformin, isotretinoin, tretinoin, topical therapy

Ming-Gui Wang,1,* Wei-Wei Huang,1,* Yu Wang,1 Yun-Xia Zhang,1 Miao-Miao Zhang,1 Shou-Quan Wu,1 Andrew J Sandford,2 Jian-Qing He1 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Centre for Heart Lung Innovation, University of British Columbia and St. Paul’s Hospital, Vancouver, BC, Canada *These authors contributed equally to this work Background: Tobacco smoking is a risk factor for tuberculosis but little is known about the relationship between tobacco smoking and drug-resistant tuberculosis (DR-TB). We undertook a systematic review and meta-analysis to quantitatively assess the association between DR-TB and tobacco smoking.Methods: We searched for relevant studies in the Ovid MEDLINE, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WANFANG, and WEIPU databases from inception to September 1, 2017. Results were expressed as odds ratios (ORs) with accompanying 95% CIs, and subgroup analyses were performed by study design, smoking type, DR-TB type, and multivariate analysis.Results: Thirty-three studies related to tobacco smoking and DR-TB were included. We found substantial evidence that tobacco smoking is associated with an increased risk of DR-TB (OR 1.57, 95% CI 1.33–1.86). Associations were also found in subgroup analyses: for multidrug-resistant tuberculosis (OR 1.49, 95% CI 1.19–1.86) and for any DR-TB (OR 1.70, 95% CI 1.3–2.23); the pooled OR was 1.45 (95% CI 1.11–1.90) for current smoking, 2.25 (95% CI 1.46–3.47) for past smoking, and 1.56 (95% CI 1.22–1.98) for smoking history; and similar ORs were also observed in study design and multivariate analysis subgroup analysis.Conclusion: This study demonstrated that tobacco smoking is an independent risk factor for DR-TB. Keywords: tobacco smoking, drug-resistant tuberculosis, multidrug-resistant tuberculosis, MDR-TB, meta-analysis

Pyoderma gangrenosum is a rare autoinflammatory skin disease. Treatment is multifactorial, addressing inflammation, pain, underlying disease, if present, and the wound. Gentian violet has been used for hundreds of years in a variety of dermatologic conditions for its anti-inflammatory properties. This study aims to evaluate gentian violet in wound healing for pyoderma gangrenosum. We conducted a retrospective chart review of patients with pyoderma gangrenosum treated with gentian violet at the Wake Forest School of Medicine Department of Dermatology in the last 10 years. The primary outcome was clinical improvement. Of the 34 cases that met inclusion criteria, 70% improved with gentian violet, 24% had no documented change, 3% initially improved then worsened, and 3% had unclear results. Gentian violet is a safe and cheap treatment that may improve resolution of pyoderma gangrenosum lesions in addition to systemic therapy.

Seven new polyketide compounds, four naphthoquinone derivatives, neofusarubins A-D ( 1 , 3 , 5 , and 18 ) and three graminin-like compounds, fusofuranones A-C ( 19 - 21 ), together with 14 known naphthoquinone derivatives, were isolated from the solid fermentation of Fusarium solani , an endophytic fungus obtained from medicinal plant as tea, Camellia chrysantha . The structures of new compounds were elucidated based on chemical evidence and spectral data analysis (1D and 2D-NMR, HR-ESI-MS, ECD, SC-XRD). Among the isolated compounds tested, 2-acetonyl-3-methyl-5-hydroxy-7-methoxy-naphthazarin ( 11 ) exhibited the most potent inhibitory activity against pancreatic cancer in PANC-1, MiaPaCa-2, and BxPC-3 cells. Network pharmacology analysis revealed that compound 11 inhibited cell proliferation and promotion of apoptosis by targeting epidermal growth factor receptor (EGFR), which were confirmed by cellular thermal shift assay (CETSA), microscale thermophoresis (MST) and EGFR stably knockdown cells model assay, respectively. In addition, molecular mechanism studies in vitro showed that 11 could suppress the growth of pancreatic cancer cells by targeting EGFR and effectively inhibit downstream PI3K/Akt signaling pathway. Collectively, these findings provide a new EGFR targeting natural product for the treatment of pancreatic cancer.

Objective: We aimed to assess the secular trends in cardiovascular health (CVH) among U.S. adults with different glycemic statuses based on the Life's Essential 8 (LE8)., Methods: This cross-sectional study used nationally representative data from 6 cycles of the National Health and Nutrition Examination Surveys between 2007 and 2018. Survey-weighted linear models were used to assess time trends in LE8 scores. Stratified analyses and sensitivity analyses were conducted to validate the stability of the results., Results: A total of 23,616 participants were included in this study. From 2007 to 2018, there was no significant improvement in overall CVH and the proportion of ideal CVH among participants with diabetes and prediabetes. We observed an opposite trend between health behavior and health factors in the diabetes group, mainly in increasing physical activity scores and sleep scores (P for trend<0.001), and declining BMI scores [difference, -6.81 (95% CI, -12.82 to -0.80)] and blood glucose scores [difference, -6.41 (95% CI, -9.86 to -2.96)]. Dietary health remained at a consistently low level among participants with different glycemic status. The blood lipid scores in the prediabetes group improved but were still at a lower level than other groups. Education/income differences persist in the CVH of participants with diabetes or prediabetes, especially in health behavior factors. Sensitivity analyses of the absolute difference and change in proportion showed a consistent trend., Conclusions: Trends in CVH among participants with diabetes or prediabetes were suboptimal from 2007 to 2018, with persistent education/income disparities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The spin degrees of freedom is crucial for the understanding of any condensed matter system. Knowledge of spin-mixing mechanisms is not only essential for successful control and manipulation of spin qubits, but also uncovers fundamental properties of investigated devices and material. For electrostatically defined bilayer graphene quantum dots, in which recent studies report spin-relaxation times T&#95;{1} up to 50 ms with strong magnetic field dependence, we study spin-blockade phenomena at charge configuration (1,2)↔(0,3). We examine the dependence of the spin-blockade leakage current on interdot tunnel coupling and on the magnitude and orientation of externally applied magnetic field. In out-of-plane magnetic field, the observed zero-field current peak could arise from finite-temperature cotunneling with the leads; though involvement of additional spin- and valley-mixing mechanisms are necessary for explaining the persistent sharp side peaks observed. In in-plane magnetic field, we observe a zero-field current dip, attributed to the competition between the spin Zeeman effect and the Kane-Mele spin-orbit interaction. Details of the line shape of this current dip, however, suggest additional underlying mechanisms are at play.

A Rh(III)-catalyzed annulation of 2-arylbenzimidazoles with α-diazo carbonyl compounds via C-H activation/carbene insertion/intramolecular cyclization is explored. The switchable product selectivity is achieved by the use of distinct α-diazo carbonyl compounds. Benzimidazole-fused quinolines are obtained through [4 + 2] annulation exclusively when 2-diazocyclohexane-1,3-diones are used, where they act as a C2 synthon. Alternatively, diazonaphthalen-1(2 H )-ones merely function as a one-carbon unit synthon to generate a quaternary center through [4 + 1] cyclization to afford spirocyclic benzimidazole-fused isoindole naphthalen-2-ones. A thorough mechanistic study reveals the course of the reaction.

We implement circuit quantum electrodynamics (cQED) with quantum dots in bilayer graphene, a maturing material platform that can host long-lived spin and valley states. Our device combines a high-impedance ( Z r ≈ 1 kΩ) superconducting microwave resonator with a double quantum dot electrostatically defined in a graphene-based van der Waals heterostructure. Electric dipole coupling between the subsystems allows the resonator to sense the electric susceptibility of the double quantum dot from which we reconstruct its charge stability diagram. We achieve sensitive and fast detection of the interdot transition with a signal-to-noise ratio of 3.5 within 1 μs integration time. The charge-photon interaction is quantified in the dispersive and resonant regimes by comparing the resonator response to input-output theory, yielding a coupling strength of g /2π = 49.7 MHz. Our results introduce cQED as a probe for quantum dots in van der Waals materials and indicate a path toward coherent charge-photon coupling with bilayer graphene quantum dots.

The global obesity problem is becoming increasingly serious, with eight of the top ten causes of death in Taiwan in 2020 being related to obesity. Morbid obesity poses a significant threat to one's health and well-being. In recent years, bariatric surgery has emerged as a more effective treatment option for patients with morbid obesity. However, the procedure is not without risks. This study aims to examine the factors that impact the postoperative efficacy evaluation of patients with morbid obesity. This study uses a retrospective cross-sectional design, with medical records being collected retrospectively. The data was collected from patients who underwent bariatric surgery between July 1, 2017 and June 30, 2020 at a hospital in southern Taiwan. A total of 663 patients were included in the study and were observed for 1 year after the surgery. The independent variables included demographic variables, perceived symptoms variables, perceived lifestyle variables, and surgery-related variables, while the dependent variables included weight loss outcomes and complications. The prognostic factors affecting the postoperative efficacy evaluation of patients with pathological obesity were determined using multiple regression analysis and binary regression analysis. The study found that 65.6% of the participants were female, with an average age of 36.8 years. The results of the multiple regression and binary logistic regression showed that gender, age, BMI, diabetes, and smoking habit were the predictors of postoperative weight loss. Hypertension, diabetes, liver disease, kidney disease, smoking habit, drinking habit, and operation time were the predictors of postoperative complications. The study found that the presence of the aforementioned 12 significant factors can affect the success of weight loss after surgery and the incidence of postoperative complications. This information can serve as a reference for clinical care institutions and patients to improve the postoperative efficacy evaluation., (© 2024. The Author(s).)

This study combines laboratory experiments and discrete element simulation methods to analyze the mechanism and deterioration patterns of sandstone surrounding rock voiding the bottom of a heavy-haul railway tunnel. It is based on previously acquired measurement data from optical fiber grating sensors installed in the Taihangshan Mountain Tunnel of the Wari Railway. By incorporating rock particle wastage rate results, a method for calculating the peak strength and elastic modulus attenuation of surrounding rock is proposed. Research indicates that the operation of heavy-haul trains leads to an instantaneous increase in the dynamic water pressure on the bottom rock ranging 144.4-390.0%, resulting in high-speed water flow eroding the rock. After 1-2 years of operation, the bottom water and soil pressures increase by 526.5% and 390.0%, respectively. Focusing on sandstone surrounding rock with high observability, laboratory experiments were conducted to monitor the degradation stages of infiltration, particle loss, and voiding of rock under the action of dynamic water flow. The impact of water flow on the "cone-shaped" bottom rock deformation was also clarified. The extent of rock deterioration and voiding was determined using miniature water and soil pressure sensors in conjunction with discrete element numerical simulations. The measured rock particle loss was used as a criterion. Finally, a fitting approach is derived to calculate the peak strength and elastic modulus attenuation of surrounding rock, gaining insight into and providing a reference for the maintenance and disposal measures for the bottom operation of heavy-haul railway tunnels., (© 2024. The Author(s).)

A stereodivergent approach toward total syntheses of Dendrobatid alkaloids 223A and 6- epi -223A is described. The approach features a concise construction of an indolizidine skeleton by Rh-catalyzed domino hydroformylation double cyclization and sequential stereocontrolled transformations such as reductive alkylation or anti -selective α-alkylation of the 5-oxoindolizidine. These stereoselective reactions afford the desired stereochemistry in the targets.

Sweet syndrome is a rare cutaneous condition with a broad clinical differential diagnosis. It can be classified into 3 subtypes: classic, malignancy-associated, and drug-induced. There are numerous associated disorders and provoking medications. Uncommonly, it can present as a multiorgan disease and cause significant morbidity. Systemic corticosteroids are the gold standard of treatment and yield rapid improvements in both lesions and symptoms. Nonsteroidal therapies may be effective alternatives, although high-quality comparative data are lacking. Some treatments for Sweet syndrome have paradoxically been implicated in the induction of disease., Competing Interests: Disclosures The authors have no relevant conflicts to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest Dr Feldman has received research, speaking and/or consulting support from a variety of companies including Galderma, GSK/Stiefel, Almirall, Leo Pharma, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Valeant, AbbVie, Samsung, Janssen, Lilly, Menlo, Merck, Novartis, Regeneron, Sanofi, Novan, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate, and National Psoriasis Foundation. He is founder and majority owner of www.DrScore.com and founder and part owner of Causa Research, a company dedicated to enhancing patients’ adherence to treatment. The other authors have no conflicts of interest to declare.

Allyl isothiocyanate (AITC) is abundant in cruciferous vegetables and it present pharmacological activity including anticancer activity in many types of human cancer cells in vitro and in vivo. Currently, no available information to show AITC affecting DNA damage and repair-associated protein expression in human gastric cancer cells. Therefore, in the present studies, we investigated AITC-induced cytotoxic effects on human gastric cancer in AGS and SNU-1 cells whether or not via the induction of DNA damage and affected DNA damage and repair associated poteins expressions in vitro. Cell viability and morphological changes were assayed by flow cytometer and phase contrast microscopy, respectively, the results indicated AITC induced cell morphological changes and decreased total viable cells in AGS and SNU-1 cells in a dose-dependently. AITC induced DNA condensation and damage in a dose-dependently which based on the cell nuclei was stained by 4', 6-diamidino-2-phenylindole present in AGS and SNU-1 cells. DNA damage and repair associated proteins expression in AGS and SNU-1 cells were measured by Western blotting. The results indicated AITC decreased nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), glutathione, and catalase, but increased superoxide dismutase (SOD (Cu/Zn)), and nitric oxide synthase (iNOS) in AGS cells, however, in SNU-1 cells are increased HO-1. AITC increased DNA-dependent protein kinase (DNA-PK), phosphorylation of gamma H2A histone family member X on Ser139 (γH2AX pSer139 ), and heat shock protein 90 (HSP90) in AGS cells. AITC increased DNA-PK, mediator of DNA damage checkpoint protein 1 (MDC1), γH2AX pSer139 , topoisomerase II alpha (TOPIIα), topoisomerase II beta (TOPIIβ), HSP90, and heat shock protein 70 (HSP70) in SNU-1 cells. AITC increased p53, p53 pSer15 , and p21 but decreased murine double minute 2 (MDM2) pSer166 and O 6 -methylguanine-DNA methyltransferase (MGMT) in AGS cells; however, it has a similar effect of AITC except increased ataxia telangiectasia and Rad 3 -related protein (ATR) pSer428 , checkpoint kinase 1 (CHK1), and checkpoint kinase 2 (CHK2) in SNU-1 cells. Apparently, both cell responses to AITC are different, nonetheless, all of these observations suggest that AITC inhibits the growth of gastric cancer cells may through induction off DNA damage in vitro., (© 2023 Wiley Periodicals LLC.)

The geographic expansion of Homo sapiens populations into southeastern Europe occurred by ∼47,000 years ago (∼47 ka), marked by Initial Upper Palaeolithic (IUP) technology. H. sapiens was present in western Siberia by ∼45 ka, and IUP industries indicate early entries by ∼50 ka in the Russian Altai and 46-45 ka in northern Mongolia. H. sapiens was in northeastern Asia by ∼40 ka, with a single IUP site in China dating to 43-41 ka. Here we describe an IUP assemblage from Shiyu in northern China, dating to ∼45 ka. Shiyu contains a stone tool assemblage produced by Levallois and Volumetric Blade Reduction methods, the long-distance transfer of obsidian from sources in China and the Russian Far East (800-1,000 km away), increased hunting skills denoted by the selective culling of adult equids and the recovery of tanged and hafted projectile points with evidence of impact fractures, and the presence of a worked bone tool and a shaped graphite disc. Shiyu exhibits a set of advanced cultural behaviours, and together with the recovery of a now-lost human cranial bone, the record supports an expansion of H. sapiens into eastern Asia by about 45 ka., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Since its initial discovery in the Hunan province of China, genomic DNA of porcine circovirus 4 (PCV4) has been detected in pigs across multiple provinces in China, as well as in South Korea. However, the prevalence of porcine circovirus type 4 in Gansu Province, China, remains unknown. To address this gap, we undertook an extensive study where we gathered 121 clinical samples displaying diverse clinical manifestations from pig farms in Gansu Province between 2022 and 2023. Employing a real-time fluorescence quantification method, we identified the presence of PCV4 genome. Out of the 121 clinical samples analyzed, 13 samples tested positive for PCV4, resulting in a positive rate of 10.74% (13/121). This finding confirms the presence of PCV4 in pig farms within Gansu Province, China. Furthermore, we successfully sequenced and analyzed the complete genomes of two distinct PCV4 strains, comparing them with 60 reference sequences archived in the GenBank database. The results revealed a high nucleotide homology (98.2-98.8%) between the strains obtained in this study and the PCV4 reference strains, indicating a relatively low evolutionary rate of the PCV4 genome. Phylogenetic analysis revealed that two strains in this study belong to PCV4a and PCV4c. As far as we know, this study marks the inaugural report on the molecular identification and genomic attributes of PCV4 in Gansu Province, China, offering valuable insights for devising preventive and control strategies against this emerging virus., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To explore the clinical potential of multiparametric cardiac magnetic resonance (CMR) in evaluating myocardial inflammation in patients with exertional heat illness (EHI)., Methods: This prospective study enrolled 28 males with EHI (18 patients with exertional heat exhaustion (EHE) and 10 with exertional heat stroke (EHS)) and 18 age-matched male healthy controls (HC). All subjects underwent multiparametric CMR, and 9 patients had follow-up CMR measurements 3 months after recovery from EHI. CMR-derived left ventricular geometry, function, strain, native T1, extracellular volume (ECV), T2, T2*, and late gadolinium enhancement (LGE) were obtained and compared among different groups., Results: Compared with HC, EHI patients showed increased global ECV, T2, and T2* values (22.6% ± 4.1 vs. 19.7% ± 1.7; 46.8 ms ± 3.4 vs. 45.1 ms ± 1.2; 25.5 ms ± 2.2 vs. 23.8 ms ± 1.7; all p < 0.05). Subgroup analysis showed that ECV was higher in the EHS patients than those in EHE and HC groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). Repeated CMR measurements at 3 months after baseline CMR showed persistently higher ECV than HC (p = 0.042)., Conclusions: With multiparametric CMR, EHI patients demonstrated increased global ECV, T2, and persistent myocardial inflammation at 3-month follow-up after EHI episode. Therefore, multiparametric CMR might be an effective method in evaluating myocardial inflammation in patients with EHI., Clinical Relevance Statement: This study showed persistent myocardial inflammation after an exertional heat illness (EHI) episode demonstrated by multiparametric CMR, which is a potential promising method to evaluate the severity of myocardial inflammation and guide return to work, play, or duty in EHI patients., Key Points: • EHI patients showed an increased global extracellular volume (ECV), late gadolinium enhancement, and T2 value, indicating myocardial edema and fibrosis. • ECV was higher in the exertional heat stroke patients than exertional heat exhaustion and healthy control groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). • EHI patients showed persistent myocardial inflammation with higher ECV than healthy controls 3 months after index CMR (22.3% ± 2.4 vs. 19.7% ± 1.7, p = 0.042)., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Hemoprotozoa are microorganisms that parasitize the blood and possess intricate life cycles. Despite the complexity of their nature, little is known about the biology of hemoprotozoa in reptilian hosts. In this study, we conducted disease surveillance on blood samples collected from six black spiny-tailed iguanas ( Ctenosaura similis ) exhibiting clinical signs. We found two different types of hemoparasites in the blood films and further confirmed they belong to the genera Lakesterella and Hepatozoon through molecular methods. In the tissue section from a dead iguana infected only with Lakesterella sp., parasites were also found in melanomacrophages of the liver and kidney. Since Lakesterella sp. infection has not been reported in C. similis , we propose this hemococcidian as a new species, Lankesterella desseri n. sp. The Hepatozoon parasites discovered in this study were classified as Hepatozoon gamezi based on their morphological characteristics, particularly the notable deformation of all infected erythrocytes, and this classification was further corroborated through molecular biological and phylogenetic analyses. This is the first hemoprotozoa investigation in C. similis with pathological and molecular characterization of these pathogens. We suggest that more studies are needed to understand the epidemiology, transmission, and impact of these parasites on their hosts and ecosystems.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV) and with a high fatality rate. Thrombocytopenia is a major clinical manifestation observed in SFTS patients, but the underlying mechanism remains largely unclear. Here, we explored the effects of SFTSV infection on platelet function in vivo in severely infected SFTSV IFNar -/- mice and on mouse and human platelet function in vitro. Results showed that SFTSV-induced platelet clearance acceleration may be the main reason for thrombocytopenia. SFTSV-potentiated platelet activation and apoptosis were also observed in infected mice. Further investigation showed that SFTSV infection induced platelet reactive oxygen species (ROS) production and mitochondrial dysfunction. In vitro experiments revealed that administration of SFTSV or SFTSV glycoprotein (Gn) increased activation, apoptosis, ROS production, and mitochondrial dysfunction in separated mouse platelets, which could be effectively ameliorated by the application of antioxidants (NAC (N-acetyl-l-cysteine), SKQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) and resveratrol). In vivo experiments showed that the antioxidants partially rescued SFTSV infection-induced thrombocytopenia by improving excessive ROS production and mitochondrial dysfunction and down-regulating platelet apoptosis and activation. Furthermore, while SFTSV and Gn directly potentiated human platelet activation, it was completely abolished by antioxidants. This study revealed that SFTSV and Gn can directly trigger platelet activation and apoptosis in an ROS-MAPK-dependent manner, which may contribute to thrombocytopenia and hemorrhage during infection, but can be abolished by antioxidants., Competing Interests: Declaration of competing interest All authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Activity or expression of sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase (SERCA) is diminished in some disease states such as cardiac failure and diabetes mellitus. A newly developed activator of SERCA, CDN1163, reportedly rescued or alleviated pathological conditions attributed to dysfunctional SERCA. We examined whether CDN1163 could relieve mouse neuronal N2A cell growth inhibition caused by cyclopiazonic acid (CPA, SERCA inhibitor). We also examined how CDN1163 affected cytosolic Ca 2+ , mitochondrial Ca 2+ and mitochondrial membrane potential., Methods: Cell viability was measured by MTT assay and trypan blue exclusion test. Cytosolic Ca 2+ , mitochondrial Ca 2+ and mitochondrial membrane potential were measured using fura 2, Rhod-2 and JC-1, respectively, as fluorescent probes., Results: CDN1163 (10 μM) itself suppressed cell proliferation, and did not alleviate CPA's inhibitory effect (and vice versa). Cell cycle was arrested at the G1 phase after CDN1163 treatment. CDN1163 treatment caused a slow yet persistent cytosolic [Ca 2+ ] elevation partly due to Ca 2+ release from an internal store other than the CPA-sensitive endoplasmic reticulum (ER). Treatment with CDN1163 for 3 h raised mitochondrial Ca 2+ level and such increase was suppressed by MCU-i4 (an inhibitor of mitochondria Ca 2+ uniporter, MCU), suggesting Ca 2+ entered the mitochondrial matrix through MCU. Treatment of cells with CDN1163 up to 2 days resulted in mitochondrial hyperpolarization., Conclusion: CDN1163 caused internal Ca 2+ leak, cytosolic Ca 2+ overload, mitochondrial Ca 2+ elevation and hyperpolarization, cell cycle arrest and cell growth inhibition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cooking events can generate household air pollutants that deteriorate indoor air quality (IAQ), which poses a threat to human health and well-being. In this study, the emission characteristics and emission factors (EFs) of air pollutants of different meats (beef, lamb, chicken, pork, and fish) cooked by a novel oil-free process and common with-oil processes were investigated. Oil-free cooking tends to emit lower total volatile organic compound (TVOC) levels and fewer submicron smoke particles and can reduce the intake of fat and calories. However, TVOC emissions during oil-free cooking were significantly different, and the lamb EFs were nearly 8 times higher than those during with-oil cooking. The particle-bound polycyclic aromatic hydrocarbon (ƩPPAH) and benzo( a )pyrene-equivalent (ƩBaP eq ) EFs during with-oil cooking ranged from 76.1 to 140.5 ng/g and 7.7-12.4 ng/g, respectively, while those during oil-free cooking ranged from 41.0 to 176.6 ng/g and 5.4-47.6 ng/g, respectively. The ƩPPAH EFs of chicken, pork, and fish were lower during oil-free cooking than during cooking with oil. Furthermore, the ƩBaP eq EFs of beef, chicken, pork, and fish were lower during oil-free cooking than during cooking with oil. Therefore, it is recommended to use the oil-free method to cook chicken, pork, and fish to reduce ƩPPAH and ƩBaP eq emissions, but not recommended to cook lamb due to the increase of ƩBaP eq emissions. The with-oil uncovered cooking EFs of aldehydes ranged from 3.77 to 22.09 μg/g, and those of oil-free cooking ranged from 4.88 to 19.96 μg/g. The aldehyde EFs were lower during oil-free covered cooking than with-oil uncovered cooking for beef, chicken, and fish. This study provides a better realizing of new cooking approaches for the reduction of cooking-induced emission, but further research on the effects of food composition (moisture and fat) and characteristics is needed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: During flight, G force compels blood to stay in leg muscles and reduces blood flow to the heart. Cardiovascular responses activated by the autonomic nerve system and strengthened by anti-G straining maneuvers can alleviate the challenges faced during G loading. To our knowledge, no definite cardiac information measured using a mobile health device exists for analyzing G tolerance. However, our previous study developed the cardiac force index (CFI) for analyzing the G tolerance of military aircrew., Objective: This study used the CFI to verify participants' cardiac performance when walking and obtained a formula for predicting an individual's G tolerance during centrifuge training., Methods: Participants from an air force aircrew undertook high-G training from January 2020 to December 2022. Their heart rate (HR) in beats per minute and activity level per second were recorded using the wearable BioHarness 3.0 device. The CFI was computed using the following formula: weight × activity / HR during resting or walking. Relaxed G tolerance (RGT) and straining G tolerance (SGT) were assessed at a slowly increasing rate of G loading (0.1 G/s) during training. Other demographic factors were included in the multivariate regression to generate a model for predicting G tolerance from the CFI., Results: A total of 213 eligible trainees from a military aircrew were recruited. The average age was 25.61 (SD 3.66) years, and 13.1% (28/213) of the participants were women. The mean resting CFI and walking CFI (WCFI) were 0.016 (SD 0.001) and 0.141 (SD 0.037) kg × G/beats per minute, respectively. The models for predicting RGT and SGT were as follows: RGT = 0.066 × age + 0.043 × (WCFI × 100) - 0.037 × height + 0.015 × systolic blood pressure - 0.010 × HR + 7.724 and SGT = 0.103 × (WCFI × 100) - 0.069 × height + 0.018 × systolic blood pressure + 15.899. Thus, the WCFI is a positive factor for predicting the RGT and SGT before centrifuge training., Conclusions: The WCFI is a vital component of the formula for estimating G tolerance prior to training. The WCFI can be used to monitor physiological conditions against G stress., (©Ming-Hao Kuo, You-Jin Lin, Wun-Wei Huang, Kwo-Tsao Chiang, Min-Yu Tu, Chi-Ming Chu, Chung-Yu Lai. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 26.07.2023.)

Herpes zoster is caused by reactivation of the latent varicella zoster virus and often occurs in immunocompromised individuals. We describe a rare case of an immunocompetent patient with herpes zoster triggered by Shingrix, a non-live vaccine designed to protect against herpes zoster. Although herpes zoster has been described as a reaction to vaccinations before, to our knowledge this is the first report of herpes zoster triggered by a varicella zoster vaccine.

Objective: This study aimed to evaluate the efficacy of different dexamethasone doses in the perioperative period of total hip arthroplasty (THA)., Patients and Methods: We randomly divided 180 patients into three groups: three perioperative saline injections (Group A, placebo); two perioperative doses of 15 mg dexamethasone plus a postoperative saline injection at 48 h (Group B); and three perioperative doses of dexamethasone (10 mg) (Group C). Primary outcomes were postoperative pain at rest and while walking. We also recorded consumption of analgesics and antiemetics, incidence of postoperative nausea and vomiting (PONV), C-reactive protein (CRP) and interleukin-6 (IL-6) levels, postoperative length of stay (p-LOS), range of motion (ROM), nausea, Identity-Consequence-Fatigue-Scale (ICFS), and severe complications (e.g., incidence of surgical site infection, SSI and gastrointestinal bleeding, GIB)., Results: Group B and C had significantly lower pain scores at rest than Group A on postoperative day 1. Group B and C also had significantly lower dynamic pain score, CRP, and IL-6 than Group A on postoperative day 1, 2, and 3. Patients in Group B and C had lower PONV incidence, reduced use of analgesics and antiemetics, improved ROM, shorter p-LOS, lower VAS nausea score, and lower ICFS than Group A patients. On postoperative day 3, patients in Group C had significantly lower dynamic pain and ICFS scores, IL-6, and CRP than Group B patients, as well as higher ROM. None of the groups exhibited SSI or GIB., Conclusions: Dexamethasone provides short-term advantages in reducing pain, PONV, inflammation, and ICFS, and increasing ROM in the early postoperative period after THA. Dexamethasone efficacy in reducing post-THA pain, inflammation, and PONV at 10 mg and 15 mg is similar during the first 48 h. Dexamethasone (30 mg) divided into three 10 mg doses was superior to two doses (15 mg) in reducing pain, inflammation, and ICFS, as well as in increasing ROM on postoperative day 3.

Competing Interests: Conflicts of interest A.A. is a consultant for AbbVie, Boehringer Ingelheim, Inflarx, Novartis, UCB, and is an investigator for Boehringer Ingelheim and Processa. W.W.H. is a consultant for Genentech. A.M. reports no conflicts of interest relevant to this manuscript. He has received consulting fees from Pfizer, Hims, Digital Diagnostics, Concert, Lilly, AbbVie, Equillium, Boehringer Ingelheim and equity from Hims, Figure 1 and Acome Seebe. He has also received licensing/royalties from Pfizer, Concert and Lilly. A.M. participates in medical advisory boards for Hims, Figure 1 and Digital Diagnostics, and has conducted clinical trials with Lilly and Concert. He is an Associate Editor for Journal of the American Medical Association Dermatology. C.A.N. has received a research grant from Boehringer Ingelheim for work outside of this manuscript. M.H.N. has received research grants from Boehringer Ingelheim for work unrelated to this manuscript. A.G.O.-L. has received consulting fees from Genentech and research grants from Pfizer, Janssen and Lilly. He has participated in advisory boards for the following companies: Janssen, Boehringer Ingelheim and Bristol Myers Squibb. He is a Section Editor for Dermatology (Karger).

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging bunyavirus, causes severe fever with thrombocytopenia syndrome (SFTS), with a high fatality rate of 20%-30%. At present, however, the pathogenesis of SFTSV remains largely unclear and no specific therapeutics or vaccines against its infection are currently available. Therefore, animal models that can faithfully recapitulate human disease are important to help understand and treat SFTSV infection. Here, we infected seven Chinese rhesus macaques ( Macaca mulatta ) with SFTSV. Virological and immunological changes were monitored over 28 days post-infection. Results showed that mild symptoms appeared in the macaques, including slight fever, thrombocytopenia, leukocytopenia, increased aspartate aminotransferase (AST) and creatine kinase (CK) in the blood. Viral replication was persistently detectable in lymphoid tissues and bone marrow even after viremia disappeared. Immunocyte detection showed that the number of T cells (mainly CD8 + T cells), B cells, natural killer (NK) cells, and monocytes decreased during infection. In detail, effector memory CD8 + T cells declined but showed increased activation, while both the number and activation of effector memory CD4 + T cells increased significantly. Furthermore, activated memory B cells decreased, while CD80 + /CD86 + B cells and resting memory B cells (CD27 + CD21 + ) increased significantly. Intermediate monocytes (CD14 + CD16 + ) increased, while myeloid dendritic cells (mDCs) rather than plasmacytoid dendritic cells (pDCs) markedly declined during early infection. Cytokines, including interleukin-6 (IL-6), interferon-inducible protein-10 (IP-10), and macrophage inflammatory protein 1 (MCP-1), were substantially elevated in blood and were correlated with activated CD4 + T cells, B cells, CD16 + CD56 + NK cells, CD14 + CD16 + monocytes during infection. Thus, this study demonstrates that Chinese rhesus macaques infected with SFTSV resemble mild clinical symptoms of human SFTS and provides detailed virological and immunological parameters in macaques for understanding the pathogenesis of SFTSV infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Huang, He, He, Wang, Lin, Zhao, Zheng and Pang.)

A rhodium(III)-catalyzed controllable [4 + 1] and [4 + 2] annulation of N -aryl pyrazolones with maleimides as C1 and C2 synthon has been explored for the synthesis of spiro[pyrazolo[1,2- a ]indazole-pyrrolidines] and fused pyrazolopyrrolo cinnolines. The product selectivity was achieved through time-dependent annulation. The [4 + 1] annulation reaction involves sequential Rh(III)-catalyzed C-H alkenylation of N -aryl pyrazolone, followed by an intramolecular spirocyclization via aza-Michael-type addition to afford spiro[pyrazolo[1,2- a ]indazole-pyrrolidine]. However, prolonged reaction time converts in situ formed spiro[pyrazolo[1,2- a ]indazole-pyrrolidine] into fused pyrazolopyrrolocinnoline. This unique product formation switch proceeds via strain-driven ring expansion through a 1,2-shift of the C-C bond.

Continuous steering movement (CSM) is an essential component of the upper extremity (UE) task during vehicle driving, and could be a suitable candidate for multi-joint rehabilitation programs for patients with UE disabilities. This study aims to evaluate the UE muscle activation during CSM and how the rotating speed and direction affect CSM's kinematic and kinetic performance. Surface electromyography (EMG), hand contact information, and steering torque were measured under fast (180°/s) and slow (60°/s) constant-velocity CSM to reveal the activation of shoulder and elbow muscles, temporal characteristics, and force exertion during the stance and swing phases of a CSM cycle. Data from 24 normal young adults showed that shorter contact duration but higher force exertion occurred in the hand moving in an outward steering direction during only fast CSM in either the clockwise (CW) or counterclockwise (CCW) direction. During a steering cycle (either fast or slow speed), the triceps brachii, sternal part of the pectoralis major (PS), and posterior deltoid play major roles in generating steering torque in the CW direction of the CSM. In contrast, the PS, clavicular part of the pectoralis major (PC), and anterior deltoid (AD) largely contribute to torque generation during the CCW CSM. During the swing phase of CSM, AD, PC, and PS are the major muscles that move the hand for the next grasping of the steering wheel in all four conditions. Using the mean activation profiles of the major contributing muscles, the functional roles of these elbow and shoulder muscles were analyzed and are discussed herein. These findings help us to further understand the activation patterns of UE muscles and the kinematic and kinetic changes during two rotating directions and two speeds of CSM, and suggest important implications for future practice in clinical training., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The aim of the study was to evaluate the efficacy of aggressive warming combined with tranexamic acid (TXA) during total hip arthroplasty (THA)., Patients and Methods: A total of 832 patients who underwent THA from October 2013 to June 2019 were divided into three groups according to the order of admission. There were 210 patients from October 2013 to March 2015 in group A, 302 patients from April 2015 to April 2017 in group B, and 320 patients from May 2017 to June 2019 in group C. Group A was the control group and was not given any measures. Group B was administered intravenously with 15 mg/kg TXA before skin incision and 3 h later without aggressive warming. Group C was administered intravenously with 15 mg/kg TXA before skin incision and 3 h later with aggressive warming. We evaluated the differences in the intraoperative blood loss, changes in core body temperature of patients at different stages during the operation, postoperative drainage, hidden blood loss, transfusion rate, drop of hemoglobin (Hb) on postoperative day 1 (POD1), prothrombin time (PT) of POD1, average hospitalization day, and complications., Results: There were statistically significant differences among the three groups during the intraoperative blood loss, intraoperative changes in core body temperature, postoperative drainage, hidden blood loss, blood transfusion rate, drop of Hb on POD1 and average hospital stay (p<0.05). There was no statistical difference in PT on POD1 and the incidence of complications (p>0.05)., Conclusions: Aggressive warming combined with TXA can significantly reduce the blood loss and transfusion rate of THA, and accelerate the recovery. We also observed that it does not increase the postoperative complications.

Bamboo nodes play a key role in the hollow structure and the rapid growth of bamboo culm. Studying on the anatomical structure of bamboo is helpful to understand its growth mechanism. Taking the noninvasive, high-resolution and accurate technical advantages of magnetic resonance imaging (MRI), we conducted cross-sectional high-resolution MRI scanning on the tip of young Moso bamboo culm (removed shoot sheath) and extracted the gray value of the MRIs by using MATLAB software to explore the differences of water distribution in nodes, proximal nodes, and internodes. The results showed that numerous vascular bundles were repeatedly twisted and rotated horizontally at the nodal diaphragms and inner wall near the nodal diaphragms of the young bamboo, forming an intricate and highly connected network. The structure protected important tissues from mechanical stress by allocating axial loads, and enabled to laterally transport water and nutrients, which was an important basis for the rapid growth of Moso bamboo in relatively short term. The signal value (also known as brightness value) of MRIs indicated that water content of vascular bundles in young bamboo culm was much higher than that of surrounding parenchyma tissues. The mean value and standard deviation of water content between pixels of internodes were significantly higher than that of nodes, and the values of that in the proximal nodes were intermediate. The development of MRI would play a significant role in the studies of bamboo anatomy, physiology, and biochemistry.

The metastasis of human osteosarcoma (OS) shows a difficult‑to‑treat clinical scenario and results in decreased quality of life and diminished survival rates. Finding or developing novel treatments to improve the life quality of patients is urgent. Bisdemethoxycurcumin (BDMC), a natural product, was obtained from the rhizome of turmeric ( Curcuma longa ) and exerts antitumor activities in numerous human cancer cell lines. At present, there is no study showing BDMC effects on OS cell migration and invasion. In the present study, the effects of BDMC on cell migration and invasion of OS U‑2 OS cells were investigated in vitro . Cell viability and proliferation were measured by flow cytometric and MTT assays, respectively. Cell motility, MMP‑2 and ‑9 activity, and cell migration and invasion were assayed by scratch wound healing, gelatin zymography, and Transwell chamber assays, respectively. The protein expression levels were measured by western blotting. BDMC at 20 and 40 µM significantly reduced total cell viability, and BDMC at 5 and 10 µM significantly inhibited cell motility in U‑2 OS cells. BDMC significantly suppressed the activities of MMP‑2 and MMP‑9 in U‑2 OS cells. BDMC suppressed cell invasion and migration after 24 h treatment in U‑2 OS cells, and these effects were in a dose‑dependently manner. Results from western blotting indicated that BDMC significantly decreased the protein expression levels of PI3K/Akt/NF‑κB, PI3K/Akt/GSK3β, and MAPK pathway in U‑2 OS cells. Furthermore, BDMC inhibited uPA, MMP‑2, MMP‑9, MMP‑13, N‑cadherin, VE‑cadherin, and vimentin but increased E‑cadherin in U‑2 OS cells. Based on these observations, it was suggested that BDMC may be a potential candidate against migration and invasion of human OS cells in the future.

Competing Interests: Conflicts of interest Dr Feldman has received research, speaking and/or consulting support from a variety of companies including Galderma, GSK/Stiefel, Almirall, Leo Pharma, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Valeant, Abbvie, Samsung, Janssen, Lilly, Menlo, Merck, Novartis, Regeneron, Sanofi, Novan, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate, and National Psoriasis Foundation; is founder and majority owner of www.DrScore.com; and is founder and part owner of Causa Research, a company dedicated to enhancing patients’ adherence to treatment. Author Hrin and Drs Bowers, Jorizzo, and Huang have no conflicts of interest to declare.

Introduction: Early diagnosis can improve melanoma prognosis. Dermoscopy can enhance early melanoma recognition., Objectives: Examine the dermoscopy features of early melanoma up to a maximum surface diameter of 6 mm., Methods: Consecutive melanoma cases were collected from two medical practices in Sydney, Australia 2019-2021. Dermoscopy features were recorded for melanomas by maximum surface diameter, to the nearest 0.1 mm, to a limit of 6 mm., Results: Total cases numbered 100; with males (N = 48) and females (N = 52), melanoma in situ (MIS, N = 96) and invasive (N = 4). The most frequent anatomic sites on both males and females were back (males N = 20, females N = 16) then knee or leg (males N = 8, females N = 12). Minimum respective MIS diameters for males/females was 1.2/2.0 mm and for invasive cases 2.0/3.4 mm. Highest frequency dermoscopy features were: light brown, dark brown, gray and asymmetric melanoma shape. Brown pigment in hair follicles were more frequent on legs compared to other anatomic sites (odds ratio [OR] 14.6; 95% CI 1.29-165.17, P 0.03). Pseudopods were substantially increased in frequency comparing diameters less than 4 mm with 4 up to 6 mm (OR 8.81; 95% CI 1.05-73.9, P 0.004). Structureless area cases recorded increased gray (OR 7.08; 95% CI 1.61-31.11, P=0.01). Melanomas with edge angulation were noted in 20%-50% of cases across diameters 1-6 mm, less frequent were pigmented circles and polygons., Conclusions: Watch out! MIS presented with a surface diameter of just 1.2 mm and invasive melanoma 2.5 mm. Pseudopods were a strong clue to melanomas with a surface diameter less than 5mm. We found melanomas on leg sites displayed more frequent pigmented hair follicles., Competing Interests: Competing Interests: None., (©2022 Pyne et al.)

Understanding the changes and influencing factors of soil organic carbon density (SOCD) during the conversion of uncultivated natural soil to croplands is of great significance for the assessment of carbon sequestration in arid areas. In this study, we compared SOCD in the uncultivated soil and that in croplands with different cultivation years (2-5, 12-15, 25-30, 40-50 years) in the Northeastern Ulan Buh Desert. The change of SOCD and its influencing factors at 0-2 m soil depth during the conversion of uncultivated natural soil to croplands were explored by the method of replacing time with space. The results showed that SOCD at the shallow soil depth (0-0.4 m) in croplands increased continuously with cultivation years, but basically at low levels (0.990-1.983 kg·m -2 ). The SOCD at deep soil (1.2-2 m) increased in the croplands with longer cultivation years (25-30 and 40-50 years), whereas no obvious change trends in both the croplands with shorter cultivation years (2-5 and 12-15 years) and the uncultivated natural soil. The SOCD at deep soil (1.2-2 m) were relatively large (28.9%-38.6%) of the 0-2 m soil depth of uncultivated natural soil and croplands with different cultivation years. The vertical distribution of SOCD in croplands with different cultivation years were well fitted by quadratic functions (with R 2 ranging from 0.757 to 0.972). It was noteworthy that soil clay and silt contents had dominant influences on SOCD at all the soil profile (0-2 m), and that cultivation years mainly contributed to the accumulation of SOC at the shallow soil (0-0.4 m).

Background: While it is known that psoriasis patients have poor adherence to both topical and systemic medications, adherence to methotrexate is not well-characterized, and ways to improve methotrexate adherence have not been addressed., Objective: The aim of this study was to evaluate whether a digital intervention improved adherence to oral methotrexate as measured by electronic monitoring., Methods: Twenty-nine patients were randomized to receive either weekly digital interventions assessing treatment adherence or no intervention for 24 weeks. Patients received medication bottles with electronic monitoring, and returned at weeks 4, 12, and 24 to evaluate disease severity., Results: The intervention group took methotrexate correctly 77.1% of the weeks observed compared to the control group which averaged 64.5%. More intervention patients took methotrexate as directed compared to the control group (78.3% vs 64.2%, p  < 0.0001). Patients were most adherent around follow-up visits, with 100% of digital intervention patients and 80% of control patients taking methotrexate correctly during the week of a follow-up visit ( p  = 0.02). The digital intervention did not significantly improve disease severity in the intervention group compared to the nonintervention group., Conclusions: Low cost, scalable digital interventions may have the potential to increase psoriasis patient adherence to methotrexate, although the mechanism for the improvement is not yet well defined.