bluuebunny/crossref_metadata_2025 huggingface dataset:
PDE4 inhibitor eliminates breast cancer stem cells via noncanonical activation of mTOR
Authors: Mukherjee Pritha , Bagchi Arka , Banerjee Ananya , Roy Himansu , Bhattacharya Arijit , Biswas Arunima , Chatterji Urmi
Published: September 2022

Ineffective cancer treatment is implicated in metastasis, recurrence, resistance to chemotherapy and radiotherapy, and evasion of immune surveillance. All these failures occur due to the persistence of cancer stem cells (CSCs) even after rigorous therapy, thereby rendering them as essential targets for cancer management. Contrary to the quiescent nature of CSCs, a gene profiler array disclosed that phosphatidylinositol‐3‐kinase (PI3K), which is known to be crucial for cell proliferation, differentiation, and survival, was significantly upregulated in CSCs. Since PI3K is modulated by cyclic adenosine 3′,5′ monophosphate (cAMP), analyses of cAMP regulation revealed that breast CSCs expressed increased levels of phosphodiesterase 4 (PDE4) in contrast to normal stem cells. In accordance, the effects of rolipram, a PDE4 inhibitor, were evaluated on PI3K regulators and signaling. The efficacy of rolipram was compared with paclitaxel, an anticancer drug that is ineffective in obliterating breast CSCs. Analyses of downstream signaling components revealed a switch between cell survival and death, in response to rolipram, specifically of the CSCs. Rolipram‐mediated downregulation of PDE4A levels in breast CSCs led to an increase in cAMP levels and protein kinase A (PKA) expression. Subsequently, PKA‐mediated upregulation of phosphatase and tensin homolog antagonized the PI3K/AKT/mTOR pathway and led to cell cycle arrest. Interestingly, direct yet noncanonical activation of mTOR by PKA, circumventing the influence of PI3K and AKT, temporally shifted the fate of CSCs toward apoptosis. Rolipram in combination with paclitaxel indicated synergistic consequences, which effectively obliterated CSCs within a tumor, thereby suggesting combinatorial therapy as a sustainable and effective strategy to abrogate breast CSCs for better patient prognosis.
The reactivity of the trapping reaction of the benzene‐bridged boron/phosphorus‐based frustrated Lewis pair with difluorocarbene and its group 14 analogs: A theoretical investigation
Authors: Zhang Zheng‐Feng , Su Ming‐Der
Published: September 2022

The trapping reactions of carbene analogsG14F2(G14 = group 14 element) by the benzene‐bridgedB/P‐Reafrustrated Lewis pair (FLPs) molecule are studied using density functional theory (B3LYP‐D3(BJ)/def2‐TZVP). Our theoretical investigations predict that only theCF2intermediate rather than other heavy carbene analogs can be trapped by theB/P‐ReaFLP‐type molecule. Energy decomposition analysis‐natural orbitals for chemical valence (EDA‐NOCV) analyses indicate that the bonding nature of theG14F2catching reactions by theB/P‐ReaFLP‐type molecule is a donor–acceptor (singlet–singlet) interaction rather than an electron‐sharing (triplet–triplet) interaction. Moreover, EDA‐NOCV and frontier molecular orbital (FMO) theory findings strongly suggest that the lone pair (LP) (P) → vacant p–π‐orbital (G14F2) interaction rather than the empty σ‐orbital (B) ← sp2‐σ‐orbital (G14F2) interaction plays a predominant role in establishing its bonding condition during theG14F2trapping reaction with theB/P‐ReaFLP‐associated molecule. Our activation strain model findings reveal that the atomic radius of the G14 element ofG14F2plays a key role in determining the activation barrier of theG14F2trapping reactions by the benzene‐bridgedB/P‐ReaFLP. The valence bond state correlation diagram (VBSCD) model developed by Shaik is used to rationalize the calculated results. The VBSCD findings demonstrate that in the present trapping reactions, the singlet triplet splitting ofG14F2plays a significant role in influencing its reaction barrier and reaction enthalpy. Our theoretical results demonstrate that the relationship between the geometrical parameters of the transition states and the corresponding reaction free energy barriers agrees well with the findings based on the Hammond postulate.
Detection of hemoglobin H disease by long molecule sequencing
Authors: Li Youqiong , Liang Liang , Qin Ting , Tian Mao
Published: September 2022

Background

Hemoglobin H (Hb H) disease is a moderate‐to‐severe form of α‐thalassemia (α‐thal), and parts of patients may require intermittent transfusion therapy, especially during intercurrent illness. However, rare Hb H diseases remain undetected using routine methods being outside of the testing scope. In this study, we present an approach to detecting Hb H disease by long molecule sequencing (LMS).

Methods

A total of 206 known genotype samples were collected and carried to blind detected by LMS on the PacBio Sequel platform. Circular consensus sequencing reads were aligned to the hg19 reference genome using Free‐Bayes finished LMS. LMS accuracy would be compared with routine methods, including Gap‐PCR and PCR‐Reverse dot blot hybridization (PCR–RDB).

Results

The assay could detect carriers of both deletion and point mutations. It had an overall accuracy of 100% when compared with routine methods. In addition, LMS detected six mutations based on routine methods and corrected three case results. Hb H diseases were identified using LMS, whether a common or rare genotype, a deletion or non‐deletion genotype. However, two cases of Hb H disease were misdiagnosed using routine methods.

Conclusions

Long molecule sequencing can be suggested as a rapid and reliable assay to detect probable carriers of hemoglobinopathies. LMS accurately identified the common and rare genotypes of Hb H disease.
Hippocampal interlamellar cell–cell connectome that counts
Authors: Pak Sojeong , Jang Doohyeong , Lee Jinho , Choi Gona , Shin Hongseong , Yang Sungchil , Yang Sunggu
Published: September 2022

The hippocampus is regarded as a cognition hub, particularly for learning and memory. Previously, neuronal mechanisms underlying various cognitive functions are delineated with the lamellar hippocampal circuitry, dentate gyrus—CA3 or CA2—CA1, within the transverse plane. More recently, interlamellar (often referred to as longitudinal) projections have received intensive attention to help understand signal convergence and divergence in cognition and behavior. Signal propagation along the longitudinal axis is evidenced by axonal arborization patterns and synaptic responses to electro‐ and photo‐stimulation, further demonstrating that information flow is more enriched in the longitudinal plane than the transverse plane. Here, we review the significance of longitudinal connections for cognition, discuss a putative circuit mechanism of place coding, and suggest the reconceptualization of the hippocampal circuitry.
Influence of Renal Function on Phosphoramide Mustard Exposure: A Nonlinear Mixed‐Effects Analysis
Authors: Jaber Mutaz M. , Takahashi Takuto , Kirstein Mark N. , Al‐Kofahi Mahmoud , Jacobson Pamala A. , Brundage Richard C.
Published: September 2022

Phosphoramide mustard (PM) is the final cytotoxic metabolite formed from the parent compound cyclophosphamide through a complex metabolic pathway, primarily through hepatic metabolism. Little is known about the effect of renal elimination on the disposition of PM. We evaluated the effect of renal function on PM exposure after single doses of cyclophosphamide in 85 patients undergoing allogeneic hematopoietic cell transplantation using nonlinear mixed‐effects modeling. Mixed linear and nonlinear elimination pathways were required to adequately describe the disposition of PM. Creatinine clearance (CrCL) was incorporated as a covariate associated with first‐order elimination, representing renal clearance (ClR) of PM. For a 70‐kg patient, ClR was 14.9 L/h, Volume of distribution was 525 L, maximum rate was 81.2 mg/h, and the concentration to achieve 50% of maximum rate was 0.51 mg/L. We conducted simulations to explore the impact of CrCL as a measure of renal function and observed that when CrCL decreases from 120 to 40 mL/min, PM area under the plasma concentration–time curve (AUC) from time 0 to 8 hours and AUC increases by 9.2% and 80.9% on average after a single dose, respectively. Our data suggest that renal function has limited influence on PM exposure during the first 8 hours after dosing but has a large impact on the total exposure. Dose adjustment of cyclophosphamide may not be necessary in hematopoietic cell transplant recipients with moderate to severe kidney dysfunction to attain targeted exposures based on AUC from time 0 to 8 hours. However, dose reduction may be necessary if demonstrated at some future time that total AUC is a better surrogate for safety or toxicity.
Sarcopenia and mild cognitive impairment among elderly adults: The first longitudinal evidence from CHARLS
Authors: Hu Yisong , Peng Wenjia , Ren Rujing , Wang Ying , Wang Gang
Published: September 2022

Background

The association between sarcopenia and mild cognitive impairment (MCI) among elderly adults in China remains unclear. The present study aimed to examine the association based on a nationally representative large‐scale survey.

Methods

The study used two waves of data from China Health and Retirement Longitudinal Study (CHARLS) in 2015 and 2018. All subjects met the inclusion criteria were classified based on Asia Working Group for Sarcopenia 2019 criteria. Aging‐associated cognitive decline is used to define MCI, and cognitive function is measured based on four dimensions: orientation, computation, memory, and drawing. OLS and logistic regression model were conducted to analyse the cross‐sectional association between sarcopenia and different cognitive functions. Logistic regression model was conducted to analyse the longitudinal association between sarcopenia and MCI.

Results

Totally, 5715 participants aged over 60 years (43.8% women; mean age 67.3 ± 6.0 years) were enrolled in a cross‐sectional association study in 2015, and further 2982 elderly adults were followed up in 2018. During the period, sarcopenia and possible sarcopenia increased from 8.5% to 29.6%. Scores of cognitive and four dimensions (orientation, computation, memory, and drawing) exhibited a decreasing trend from non‐sarcopenia to sarcopenia (P < 0.001). In the fully adjusted OLS regression model, scores of four dimensions were lower in possible sarcopenia and sarcopenia groups when compared with the non‐sarcopenia group (P < 0.05) respectively. The incidence of MCI was 10.1%, 16.5%, and 24.2% for non‐sarcopenia, possible sarcopenia, and sarcopenia groups from 2015 to 2018, with a significantly statistical difference (P < 0.001). Logistic regression model revealed an odds ratio of 1.43 [95% confidence interval (CI): 1.06–1.91, P = 0.017] for the possible sarcopenia group and 1.72 (95% CI: 1.04–2.85, P = 0.035) for sarcopenia group when compared with the non‐sarcopenia group.

Conclusions

Sarcopenia is associated with worse cognitive impairment, which provided new evidence for a strong association that warrants further research into mechanistic insights.
Understanding real‐world treatment patterns and clinical outcomes in AL amyloidosis patients diagnosed in Canada: A population‐based cohort study
Authors: Jimenez‐Zepeda Victor H. , Reece Donna , Rigo Rodrigo , Gogna Priyanka , Kong Shiying , Hu Xun Yang , Chapani Parv , Cheung Winson Y. , Brenner Darren R. , Plante Richard , Shi Kun , Husain Asad , Tankala Dipti , Boyne Devon J.
Published: September 2022

Amyloid light chain (AL) amyloidosis is a rare and chronic bone marrow disorder. Existing claims data can be used to help understand the real‐world treatment patterns and outcomes of this patient population. Various population‐based administrative databases in Alberta, Canada were queried from 2010 to mid‐2019 to identify cases of AL amyloidosis. Baseline patient and disease characteristics, sequencing of pharmacologic therapies, overall survival, and healthcare resource utilization were evaluated. A total of 215 individuals with AL amyloidosis were included. Among patients diagnosed between 2012 and 2019, 149 (85.1%) initiated first‐line, 67 (38.3%) initiated second‐line, 22 (12.6%) initiated third‐line, and 11 (6.3%) initiated fourth‐line systemic therapy. In the first‐line setting, 99/149 (66.4%) received bortezomib, cyclophosphamide, and dexamethasone (CyBorD) and 21/149 (14.1%) received another bortezomib‐based regimen. Survival from time of diagnosis improved over time, with a median overall survival of 25.8 months (95% CI: 9.8, 57.1) for individuals diagnosed in 2010–2011 versus 52.1 months (95% CI: 25.6, NA) for those diagnosed in 2012–2019. Despite this improvement, the proportion of individuals diagnosed in 2012–2019 who survived beyond five‐years remained low (5‐year survival: 48.4%; 95% CI: 40.9, 57.2) which highlights an unmet need for more efficacious therapies.
Synthesis and biological assessment of some fused Pyran derivatives
Authors: Shamili Sriramoju , Siddoju Kavitha , Srinivas Avula , Farheen Sd. Ishrath
Published: September 2022

Pyran was formed by reacting methyl 3‐methoxyacrylate (1) with 2‐benzylidenemalanonitrile to form compound 2. The pyrano derivatives 3–6 were obtained by reacting the second molecule with 2‐benzylidenemalanonitrile, carbon disulfide, formamide, and benzylidene cyclohexanone. Compound (2) interacted with ethyl chloroacetate to form compound 8, which then cyclized in the presence of sodium ethoxide to form compound 9. Compound 7 was formed when compound (2) was treated with acetic acid in the presence of sulfuric acid and reacted with ethylchloroacetate to form compound 10 and then was converted to compound 11 by the addition of sodium ethoxide. Analytical and spectral data have been used to determine the structures of the newly synthesized substances and they were then tested for their antibacterial and antioxidant activities. In terms of antioxidant activity, compounds 2 and 8 were found to have the greatest and lowest levels, respectively, against Enterobacter aerogenes.
Evolutionary functional morphology of the proboscis and feeding apparatus of hawk moths (Sphingidae: Lepidoptera)
Authors: Reinwald Caroline , Bauder Julia A.‐S. , Karolyi Florian , Neulinger Michael , Jaros Sarah , Metscher Brian , Krenn Harald W.
Published: September 2022

The morphology of the proboscis and associated feeding organs was studied in several nectar‐feeding hawk moths, as well as a specialized honey‐feeder and two supposedly nonfeeding species. The proboscis lengths ranged from a few millimeters to more than 200 mm. Despite the variation in proboscis length and feeding strategy, the principle external and internal composition of the galeae, the stipes pump, and the suction pump were similar across all species. The morphology of the smooth and slender proboscis is highly conserved among all lineages of nectar‐feeding Sphingidae. Remarkably, they share a typical arrangement of the sensilla at the tip. The number and length of sensilla styloconica are independent from proboscis length. A unique proboscis morphology was found in the honey‐feeding species Acherontia atropos. Here, the distinctly pointed apex displays a large subterminal opening of the food canal, and thus characterizes a novel type of piercing proboscis in Lepidoptera. In the probably nonfeeding species, the rudimentary galeae are not interlocked and the apex lacks sensilla styloconica; galeal muscles, however, are present. All studied species demonstrate an identical anatomy of the stipes, and suction pump, regardless of proboscis length and diet. Even supposedly nonfeeding Sphingidae possess all organs of the feeding apparatus, suggesting that their proboscis rudiments might still be functional. The morphometric analyses indicate significant positive correlations between galea lumen volume and stipes muscle volume as well as the volume of the food canal and the muscular volume of the suction pump. Size correlations of these functionally connected organs reflect morphological fine‐tuning in the evolution of proboscis length and function.
The whole‐genome sequencing of prevalent DENV‐1 strains during the largest dengue virus outbreak in Xishuangbanna Dai autonomous prefecture in 2019
Authors: Li Daiying , Long MingWang , Li Tingting , Shu Yun , Shan Xiyun , Zhang Juan , Ma Dehong , Long Shuying , Wang Xiaodan , Jia Fan , Pan Yue , Chen Junying , Liu Pinghua , Sun Qiangming
Published: September 2022

In 2019, a serious dengue virus (DENV) infection broke out in the Xishuangbanna Dai Autonomous Prefecture, China. Therefore, we conducted a molecular epidemiological analysis in people that contracted DENV serotype 1 (DENV‐1) during this year. We analyzed the molecular epidemiology of six DENV‐1 epidemic strains in 2019 by full‐length genome sequencing, amino acid mutation site analysis, evolutionary tree analysis, and recombination site comparison analysis. Through the analysis of amino acid mutation sites, it was found that DENV‐1 strain (MW386867) was different from the other five epidemic DENV‐1 strains in Xishuangbanna in 2019. MW386867 had unique mutation sites at six loci. The six epidemic DENV‐1 strains in Xishuangbanna in 2019 were divided into two clusters. MW386867 was highly similar to the MG679800 (Myanmar 2017), MG679801 (Myanmar 2017), and KC172834 (Laos 2008), and the other five strains were highly similar to JQ045660 (Vietnam 2011), FJ176780 (GuangDong 2006). Genetic recombination analysis revealed that there was no recombination signal in the six epidemic DENV‐1 strains in Xishuangbanna in 2019. We speculate that the DENV‐1 epidemic in 2019 has a co‐epidemic of local strains and cross‐border strains.
COVID‐19 immunopathology: From acute diseases to chronic sequelae
Authors: Arish Mohd , Qian Wei , Narasimhan Harish , Sun Jie
Published: September 2022

The clinical manifestation of coronavirus disease 2019 (COVID‐19) mainly targets the lung as a primary affected organ, which is also a critical site of immune cell activation by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). However, recent reports also suggest the involvement of extrapulmonary tissues in COVID‐19 pathology. The interplay of both innate and adaptive immune responses is key to COVID‐19 management. As a result, a robust innate immune response provides the first line of defense, concomitantly, adaptive immunity neutralizes the infection and builds memory for long‐term protection. However, dysregulated immunity, both innate and adaptive, can skew towards immunopathology both in acute and chronic cases. Here we have summarized some of the recent findings that provide critical insight into the immunopathology caused by SARS‐CoV‐2, in acute and post‐acute cases. Finally, we further discuss some of the immunomodulatory drugs in preclinical and clinical trials for dampening the immunopathology caused by COVID‐19.
Native and activated antithrombin inhibits TMPRSS2 activity and SARS‐CoV‐2 infection
Authors: Wettstein Lukas , Immenschuh Patrick , Weil Tatjana , Conzelmann Carina , Almeida‐Hernández Yasser , Hoffmann Markus , Kempf Amy , Nehlmeier Inga , Lotke Rishikesh , Petersen Moritz , Stenger Steffen , Kirchhoff Frank , Sauter Daniel , Pöhlmann Stefan , Sanchez‐Garcia Elsa , Münch Jan
Published: September 2022

Host cell proteases such as TMPRSS2 are critical determinants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) tropism and pathogenesis. Here, we show that antithrombin (AT), an endogenous serine protease inhibitor regulating coagulation, is a broad‐spectrum inhibitor of coronavirus infection. Molecular docking and enzyme activity assays demonstrate that AT binds and inhibits TMPRSS2, a serine protease that primes the Spike proteins of coronaviruses for subsequent fusion. Consequently, AT blocks entry driven by the Spikes of SARS‐CoV, MERS‐CoV, hCoV‐229E, SARS‐CoV‐2 and its variants of concern including Omicron, and suppresses lung cell infection with genuine SARS‐CoV‐2. Thus, AT is an endogenous inhibitor of SARS‐CoV‐2 that may be involved in COVID‐19 pathogenesis. We further demonstrate that activation of AT by anticoagulants, such as heparin or fondaparinux, increases the anti‐TMPRSS2 and anti‐SARS‐CoV‐2 activity of AT, suggesting that repurposing of native and activated AT for COVID‐19 treatment should be explored.
Shank3 influences mammalian sleep development
Authors: Medina Elizabeth , Schoch Hannah , Ford Kaitlyn , Wintler Taylor , Singletary Kristan G. , Peixoto Lucia
Published: September 2022

Sleep problems are prevalent in autism spectrum disorder (ASD), can be observed before diagnosis, and are associated with increased restricted and repetitive behaviors. Therefore, sleep abnormalities may be a core feature of the disorder, but the developmental trajectory remains unknown. Animal models provide a unique opportunity to understand sleep ontogenesis in ASD. Previously we showed that adult mice with a truncation in the high‐confidence ASD gene Shank3 (Shank3∆C) recapitulate the clinical sleep phenotype. In this study we used longitudinal electro‐encephalographic (EEG) recordings to define, for the first time, changes in sleep from weaning to young adulthood in an ASD mouse model. We show that Shank3∆C male mice sleep less overall throughout their lifespan, have increased rapid eye movement (REM) sleep early in life despite significantly reduced non‐rapid eye movement (NREM) sleep, and have abnormal responses to increased sleep pressure that emerge during a specific developmental period. We demonstrate that the ability to fall asleep quickly in response to sleep loss develops normally between 24 and 30 days in mice. However, mutants are unable to reduce sleep latency after periods of prolonged waking and maintain the same response to sleep loss regardless of age. This phenomenon seems independent of homeostatic NREM sleep slow‐wave dynamics. Overall, our study recapitulates both preclinical models and clinical studies showing that reduced sleep is consistently associated with ASD and suggests that problems falling asleep may reflect abnormal development of sleep and arousal mechanisms.
Cervical disc arthroplasty combined with two‐level ACDF for the treatment of contiguous three‐level cervical degenerative disc disease: A comparative study
Authors: Huang Kangkang , Liu Hao , Wang Beiyu , Wu Tingkui , Ding Chen , He Junbo , Meng Yang , Wang Han , Hong Ying
Published: September 2022

To compare the differences among constructs with one‐level cervical disc arthroplasty (CDA) and two‐level anterior cervical discectomy and fusion (ACDF). A retrospective study was conducted involving patients who underwent one‐level CDA and two‐level ACDF between June 2012 and July 2020. According to the different locations of CDA and ACDF, we divided the constructs into three types: type Ⅰa: CDA‐ACDF‐ACDF; type Ⅰb: ACDF‐CDA‐ACDF; type Ⅰc: ACDF‐ACDF‐CDA. The differences of clinical and radiological outcomes were evaluated. Fifty‐three patients were included with 29 in type Ⅰa group, 11 in type Ⅰb group, and 13 in type Ⅰc group. After surgery, all groups showed significant improvement in apanese Orthopedic Association, Neck Disability Index, and Visual Analog Scale scores (p < 0.001). Range of motion (ROM) of the total cervical spine in type Ⅰc group decreased significantly compared with those in type Ⅰa and type Ⅰb groups (p < 0.05). No significant differences in ROM of the arthroplasty segment and the variations in ROM of the superior adjacent segment were observed among the three groups. The fusion rates of the superior ACDF segments were significantly higher at 6 and 12 months postoperatively than those of the inferior ACDF segments (p < 0.05). The clinical outcomes were similar among constructs concerning different locations of CDA and ACDF in three‐level hybrid surgery. ROM of the cervical spine in type Ⅰc group decreased significantly compared with that in type Ⅰa and type Ⅰb groups. The fusion rates of superior ACDF segments were higher at early time points after surgery than those of inferior ACDF segments.
Vasculogenic gene therapy: No role for revitalization of structural bone allografts
Authors: Rezaie Elisa S. , Visser Noortje J. , van den Berg Catherine , Shin Alexander Y. , Bishop Allen T.
Published: September 2022

Segmental bone defects are often performed with cryopreserved allografts. They provide immediate stability, but risk nonunion, infection and late stress fracture. Improving the rate and extent of bone revitalization may improve results. Angiogenesis from surgically placed arteriovenous (AV) bundles improves bone blood flow and vitality in cryopreserved rat femora, augmented by vasculogenic growth factors. This study tests the same principal in Yucatan mini‐pigs with a tibial diaphyseal defect, combining surgical angiogenesis with angiogenic gene therapy within cryopreserved orthotopically‐placed allografts. Tibial diaphyseal defects were reconstructed with cryopreserved allografts and rigid internal fixation in 16 mini pigs. Half of the cranial tibial AV bundles placed within the allograft medullary canal were transfected with an adeno‐associated virus containing vascular endothelial growth factor (VEGF) and platelet‐derived growth factor (PDGF) genes (AAV9.VEGF.PDGF). Bone remodeling, angiogenesis, and allograft healing were assessed. During the postoperative survival period 5 of 8 transfected animals developed cutaneous benign vascular lesions at sites remote from the operated hindlimb, causing excessive bleeding. Within the allograft, both medullary (p = 0.013) and cortical (p = 0.009) vascular volumes were higher and vessels more mature than nontransfected allografts. Bone turnover (p = 0.013), bone mineralization (p = 0.018), bone healing (p = 0.008) and graft incorporation (p = 0.006) were all significantly higher in the gene therapy group. In a large animal tibial defect model, gene therapy of implanted AV bundles improved revascularization, remodeling and healing of cryopreserved allografts used for limb reconstruction. However, benign vascular lesions causing excessive bleeding developed in 5 out of 8 pigs transfected with AAV containing genes for VEGF and PDGF. This unforeseen complication makes vasculogenic gene therapy unacceptable for clinical use.
Age‐related decrease in periostin expression may be associated with attenuated fracture healing in old mice
Authors: Clark Daniel , Doelling Jeffrey , Hu Diane , Miclau Theodore , Nakamura Mary , Marcucio Ralph
Published: September 2022

Older adults suffer more bone fractures with higher rates of healing complications and increased risk of morbidity and mortality. An improved understanding of the cellular and molecular mechanism of fracture healing and how such processes are perturbed with increasing age may allow for better treatment options to manage fractures in older adults. Macrophages are attractive therapeutics due to their role in several phases of fracture healing. After injury, bone marrow–derived macrophages are recruited to the injury and propagate the inflammatory response, contribute to resolution of inflammation, and promote bone regeneration. A tissue resident population of macrophages named osteal macrophages are present in the periosteum and are directly associated with osteoblasts and these cells contribute to bone formation. Here, we utilized bulk RNA sequencing to analyze the transcriptional activity of osteal macrophages from old and young mice present in primary calvarial cultures. Macrophages demonstrated a diverse transcriptional profile, expressing genes involved in immune function as well as wound healing and regeneration. Periostin was significantly downregulated in macrophages from old mice compared to young. Periostin is an extracellular matrix protein with important functions that promote osteoblast activity during bone regeneration. An age‐related decrease of periostin expression was verified in the fracture callus of old mice compared to young. Young periostin knockout mice demonstrated attenuated fracture healing outcomes that reflected what is observed in old mice. This study supports an important role of periostin in fracture healing, and therapeutically targeting the age‐related decrease in periostin may improve healing outcomes in older populations.
Unravelling pine response to Fusarium circinatum through Raman spectroscopy
Authors: Martín Daniel , Santos Inês P. , Monteiro Pedro , Amaral Joana , da Costa Ricardo M. F. , Martín‐Garcia Jorge , Batista de Carvalho Luís A. E. , Marques Maria Paula M. , Pinto Glória
Published: September 2022

Pine Pitch Canker (PPC), caused by the fungus Fusarium circinatum, is associated to significant economic and ecological losses worldwide. The effectiveness of PPC monitoring, early detection in nurseries and plantations, and the identification of resistant plant material relies on the development of objective, non‐destructive, and cost‐effective tools. This study analyzed the potential of employing Raman Spectroscopy (RS) for the early detection of biochemical changes associated with PPC in Pinus spp. with different susceptibilities to F. circinatum (highly susceptible Pinus radiata vs relatively resistant Pinus pinea), while unveiling possible mechanisms of action on these pathosystems. Our results indicate lignin as a key constitutive component of pine resistance against PPC and thus the potential of using this technology for the selection of PPC resistant trees. Moreover, we demonstrate the power of RS‐based approaches for the rapid detection of the disease in susceptible species. Early spectral variations were found in P. radiata upon inoculation with F. circinatum from 3 days post‐inoculation (dpi) onwards, whereas changes in histological analysis, relative internal stem necrosis measurements, and visual disease symptoms were only visible at 6, 8, and 9 dpi, respectively. These spectral changes have been associated to cell wall degradation and induction of phenolic compounds synthesis upon infection in P. radiata. Altogether, we believe that RS is an innovative promising tool able to reduce disease detection time in pine species and providing an appealing alternative for the development of new and eco‐friendly disease control measures.
Ultrasound‐Guided Capsular Thyroid Injection Therapy With Dexamethasone and Lidocaine Mixture for Subacute Thyroiditis
Authors: Huo Jinlong , Chen Chen , Gao Dan , Yang Li , Qu Rui , Jiang Hang , Chen Xin , Guo Youming , Zhu Shuanghong , Ou Dong , Zhao Lijin
Published: September 2022

Objectives

Subacute thyroiditis (SAT) is a self‐limiting, inflammatory thyroid disease possibly caused by viral infection. In recent years, the incidence of SAT is increasing, especially during the pandemic of the COVID‐19. This study aimed to evaluate the efficacy, safety, and recovery time of capsular thyroid injection therapy under ultrasound guidance for SAT.

Methods

A total of 73 patients with SAT were divided into two groups. Patients in group A (n = 48) received an ultrasound‐guided capsular injection consisting of dexamethasone (DEX) and lidocaine in the thyroid lesion area, while patients in group B (n = 25) received oral prednisolone (PSL). The two groups were compared for pain relief and treatment duration, the recovery time of thyroid function, recurrence rates, hypothyroidism incidence, and drug‐related side effects.

Results

The follow‐up time was 1 year. In group A, the duration of pain relief, treatment, and recovery time of thyroid function were significantly shorter than that in group B (P < .05), and no statistically significant differences in recurrence rate or incidence of hypothyroidism were observed (P > .05). Weight gain was significantly higher in group A at the end of treatment (P < .001).

Conclusions

Compared with oral PSL treatment, ultrasound‐guided local injection of DEX and lidocaine into the capsular thyroid is a safe and effective procedure that can significantly reduce the treatment time of SAT.
Advancements in the diagnosis and treatment of renal epithelioid angiomyolipoma: A narrative review
Authors: Yang Jian‐Wei , Liang Cheng , Yang Li
Published: September 2022

Renal epithelioid angiomyolipoma (EAML) is a unique subtype of angiomyolipoma that contains a variety of cytoplasmic‐rich, eosinophilic cytoplasm epithelioid cells in addition to mature adipocytes, hyaline thick‐walled vessels, and smooth muscle‐like spindle cells. In recent years, increasing evidence has shown that EAML is a potentially malignant tumor. Due to the lack of typical clinical manifestations and imaging features, it is difficult to diagnose before surgery, and the diagnosis mainly depends on postoperative histopathological examination. With the advancement of pathological diagnostic techniques, more EAML cases has been discovered, but clinicians still lack a comprehensive understanding of EAML. This review comprehensively describes some pathological and clinical features of EAML, with special attention to the pathogenesis and treatment of malignant EAML in order to assist with clinical diagnosis and treatment.
Changes in quantity and quality of dissolved organic carbon in purple soil: Roles of land use and soil depth
Authors: Liang Ke , Bi Yunfei , He Binghui , Feng Mengdie , Xi Peidong , Li Tianyang
Published: September 2022

Dissolved organic carbon (DOC) is the substrate for microbial activities and regulates the biogeochemical cycle of carbon. Considerable areas of croplands have been converted to secondary forest and economic plantation following the implementation of Grain‐for‐Green Program projects in China, markedly altering the quantity and quality of topsoil DOC. However, the extent and magnitude of these land use changes affecting soil DOC remain largely unclear. This study aimed to elucidate the effects of different land uses and soil depths on topsoil DOC quantity and quality. Soil samples were collected from secondary forest (SF), orchards/plantations (OP), and cropland (CL) at 0–5, 5–10, 10–15, and 15–20 cm soil depths, respectively, from a representative purple soil hillslope, Southwest China. Soil DOC concentration and related UV–visible absorbance characteristics were determined to assesss respectively the quantity and quality of DOC. Results showed that DOC concentration was 44% lower in the OP than in the SF and CL. Higher ratios of UV absorbance value at 254, 260, and 400 nm to DOC concentration (i.e., SUAV254, SUVA260, and C:C ratio), electronic conductivity (EC), cation exchange capacity (CEC), soil organic carbon (SOC), and total nitrogen (TN) concentration were found in the OP rather than in the SF and CL. The SUAV254, SUVA260, SOC, and TN concentration were the highest at 0–5 cm soil depth. DOC concentration showed negative relationships with most UV absorbance values, SUAV254, SUVA260, and C:C ratio. Soil EC, CEC, and pH were closely correlated with the DOC concentration and its UV–visible variables. Our results indicated that DOC was relatively richer in aromatic and humic substances in the OP, providing valuable information for sustainable ecological restoration and land use management.
Spatial–temporal variation analysis of water storage and its impacts on ecology and environment in high‐intensity coal mining areas
Authors: Sun Yilin , Jiang Jinbao , Yang Fei , Chen Xuhui , Yu Zijian , Guo Qiyu , Zhao Yinpeng
Published: September 2022

In common with other important coal bases in northwestern China, the hydrology and ecology and environment of Ordos, northern Shaanxi (Shanbei), and Shanxi Provinces have much. Terrestrial water storage anomaly (TWSA), soil moisture anomaly (SMA), and groundwater storage anomaly (GWSA), are important water storage qualities that play a critical role in the distribution and growth of vegetation. In this paper, multi‐source remote sensing data were used to analyze the spatial–temporal changes and relationships of water storage, ecology and environment from 2002 to 2020. The numerical results showed the TWSA and GWSA in the study area had a declining trend and the rates were −7.512 mm yr‐1 and −8.268 mm yr‐1, respectively. On the contrary, the SMS showed an increasing trend, and the rate was 0.840 mm yr‐1. By trend variation and correlation analysis, we found GWSA is the main part in the variation of TWSA. By further analysis, it was found that the climate factors are not the major factors causing the variation of GWSA, but coal mining and artificial irrigation activities, which are especially clear in the Taihang Mountains in eastern Shanxi Province. The ecology and environment have been improving, and water storage and climate factors have played a different role in different regions. The warm climate conditions and the increased 0–40 cm of soil water have promoted the growth of vegetation and the improvement of the ecology and environment. The research results are helpful to understand the impacts of water storage on the ecology and environment in high‐intensity coal mining areas.
Sponge contribution to the silicon cycle of a diatom‐rich shallow bay
Authors: López‐Acosta María , Maldonado Manuel , Grall Jacques , Ehrhold Axel , Sitjà Cèlia , Galobart Cristina , Pérez Fiz F. , Leynaert Aude
Published: September 2022

In coastal systems, planktonic and benthic silicifiers compete for the pool of dissolved silicon, a nutrient required to make their skeletons. The contribution of planktonic diatoms to the silicon cycle in coastal systems is often well characterized, while that of benthic silicifiers such as sponges has rarely been quantified. Herein, silicon fluxes and stocks are quantified for the sponge fauna in the benthic communities of the Bay of Brest (France). A total of 45 siliceous sponge species living in the Bay account for a silicon standing stock of 1215 tons, while that of diatoms is only 27 tons. The silicon reservoir accumulated as sponge skeletons in the surface sediments of the Bay rises to 1775 tons, while that of diatom skeletons is only 248 tons. These comparatively large stocks of sponge silicon were estimated to cycle two orders of magnitude slower than the diatom stocks. Sponge silicon stocks need years to decades to be renewed, while diatom turnover lasts only days. Although the sponge monitoring over the last 6 yr indicates no major changes of the sponge stocks, our results do not allow us to conclude if the silicon sponge budget of the Bay is at steady state, and potential scenarios are discussed. The findings buttress the idea that sponges and diatoms play contrasting roles in the marine silicon cycle. The budgets of these two major silicon users need to be integrated and their connections revealed, if we aim to improve our understanding of the silicon cycling in coastal ecosystems.
DOC, grazers, and resilience of phytoplankton to enrichment
Authors: Carpenter Stephen R. , Pace Michael L. , Wilkinson Grace M.
Published: September 2022

Phytoplankton blooms often follow nutrient enrichment. Differences among lakes in light‐absorbing dissolved organic carbon (DOC) may shift bloom thresholds to higher nutrient loads and thereby increase resilience of lakes to enrichment. To explore this idea, we measured resilience to experimental enrichment of two lakes with contrasting DOC concentrations. We compared bloom thresholds in both lakes using a model of phytoplankton response to DOC and nutrients, a dynamic time series indicator of resilience, and two empirical measures of stochastic resilience, mean exit time and median survival time. For the dynamic indicator and ecosystem model the lake with higher DOC was more resilient to enrichment. However, the distributions overlapped for stochastic indicators of resilience of the two lakes. These analyses show that DOC interacts with mixing depth and zooplankton biomass to affect resilience. Strong contrasts in DOC and many observations are needed to discern effects of DOC on resilience to enrichment.
Progress in Chemical Recycling of Carbon Fiber Reinforced Epoxy Composites
Authors: Liu Tuan , Shao Lin , Zhao Baoming , Chang Yu‐Chung , Zhang Jinwen
Published: September 2022

Carbon fiber reinforced polymer (CFRP) composites are indispensable in a variety of applications, because of their high specific strength. CFRPs are generally constructed by carbon fibers as reinforcements and crosslinked polymers as binders. Due to the irreversible nature of the crosslinked polymers, CFRPs are neither repairable nor recyclable. Once the material is damaged or out of service, landfill or incineration is the typical way to deal with the waste. These methods take no advantages of the residue value of the waste and add burdens to the environment. To reduce waste and cost, it is desirable to develop effective recycling technologies to reserve the residue value of carbon fiber and polymer matrix. In the past decade, chemical recycling by cleaving the covalent bonds in a solvent has been considered as an ideal path for the recycling of CFRP wastes, because it has the potential to recover both valuable CFs and polymer matrix. In this review, the discussion is focused on the progress in the chemical recycling of CFRP. The primary matrix resin of CFRP discussed in this review is epoxy resin which is the most widely used polymer matrix. In addition, the challenges and outlook are provided.
Impact of asset preferences on firm performance over its life cycle: Is agency theory or neo‐classical theory more relevant?
Authors: Ramzan Muhammad , Lau Wee‐Yeap
Published: September 2022

This study extends Dickinson's (2011) firm life cycle classification approach by linking it with the asset preferences and firm performance. This study also resolves the contention between agency theory and neo‐classical theory. Based on the data of S&P 500 firms from 2000 to 2019, our results show: First, the effect of current assets on basic earnings per share (BEPS), return on assets (ROA) and Tobin's Q ratio (TQR) decreases from the introduction to decline stage. Second, the influence of fixed assets on TQR increases from the introduction to the declining stage. Our findings suggest that both theories are relevant, and asset acquisition influences the productivity and performance of the firms.
Uric Acid in Parkinson′s Disease: What Is the Connection?
Authors: Seifar Fatemeh , Dinasarapu Ashok R. , Jinnah H. A.
Published: September 2022

Numerous studies have linked Parkinson′s disease (PD) with low levels of uric acid (UA). Low UA has been associated with the risk of developing PD, and its progression and severity. The biological mechanisms underlying these relationships have never been firmly established. The most frequently proposed mechanism is that UA is an antioxidant. Low UA is thought to predispose to oxidative stress, which contributes to dopamine neuron degeneration, and leads to initial appearance of symptoms of PD and its worsening over time. Several recent studies have questioned this explanation. In this review, we describe the biology of UA, its many links with PD, evidence regarding UA as an antioxidant, and we question whether UA causes PD or contributes to its progression. We also address the possibility that something about PD causes low UA (reverse causation) or that low UA is a biomarker of some other more relevant mechanism in PD. We hope the evidence provided here will stimulate additional studies to better understand the links between UA and PD. Elucidating these mechanisms remains important, because they may provide new insights into the pathogenesis of PD or novel approaches to treatments. © 2022 International Parkinson and Movement Disorder Society.
Advanced controller design for uncertain linear systems with time‐varying delays via augmented zero equality approach
Authors: Lee Yonggwon , Kim Yeongjae , Kim Seungho , Lee Seunghoon , Park Myeongjin , Kwon Ohmin
Published: September 2022

This paper deals with the stability analysis and controller design for linear systems with time‐varying delays and parameter uncertainties. By choosing appropriate augmented Lyapunov–Krasovskii functionals, a set of linear matrix inequalities is derived to get advanced feasible region of stability and controller gain matrices that guarantee the asymptotic stability of the concerned systems within maximum bound of time delays and its time derivative. To further reduce the conservatism of stabilization criterion, a recently developed mathematical technique that constructed a new augmented zero equality is applied. Finally, two numerical examples are utilized to show the validity and superiority of the proposed methods.
A probability distribution for precipitation data analysis
Authors: Khadim Aneeqa , Hussain Tassaddaq , Bakouch Hassan S. , Saghir Aamir
Published: September 2022

Hydrologic design is often based on assessments of large return interval measures; it is vital to be able to conclude them as precisely as possible. Henceforth, the selection of a probability distribution is very crucial for such cases. In view of this scenario, we propose and study a pliant probability distribution for precipitation data analysis. Some mathematical and statistical properties are analyzed. In order to make stronger predictions and judge the realistic return period, we have also characterized the model via Laplace transformation. We have estimated its parameters via the maximum likelihood estimation and constructed its information matrix for developing the confidence belt of population parameters. Moreover, a real‐life setup is also considered by applying the model over precipitation data of diverse regions, including Jacksonville, Florida (USA), Barkhan (Pakistan), British Columbia (Canada), and Alexandria (Egypt). This investigated study is based on various statistical parametric and nonparametric tests, which indicates that the proposed model is one of the better strategies for precipitation data analysis when compared with the famous three‐parameter Kappa model.
Ultra‐wideband metamaterial absorber based on frequency selective resistive film for 5G spectrum
Authors: Ruan Jiu F. , Meng Zi F. , Zou Rui Z. , Pan Sheng M. , Ji Sheng W.
Published: September 2022

An ultra‐wideband metamaterial absorber (MA) is proposed for 5G communication, which features a resistive frequency selective surface printed on a PET (polyethylene terephthalate) layer and a ground layer of resistive film. The proposed MA can provide over 90% absorptivity in the frequency range of 11.2–42.8 GHz. Moreover, it is insensitive to polarization and wide incident angles. The effective medium theory and multi‐reflection interference theory are used to interpret the broadband absorption mechanism. The surface current distribution at three absorption peaks is investigated to further study the physical mechanism behind the wideband absorption. The measured results of the fabricated prototype are in good agreement with the simulation ones, thus verifying the robustness of the design. The presented MA can probably be used in electromagnetic shielding of 5G signals.
Update on artificial insemination: Semen, techniques, and sow fertility
Authors: Mellagi Ana P. G. , Will Kelly J. , Quirino Monike , Bustamante‐Filho Ivan C. , Ulguim Rafael da R. , Bortolozzo Fernando P.
Published: September 2022

Over the years, reproductive efficiency in the swine industry has focused on reducing the sperm cell number required per sow. Recent advances have included the identification of subfertile boars, new studies in extended semen quality control, new catheters and cannulas for intrauterine artificial insemination (AI), and fixed‐time AI under commercial use. Therefore, it is essential to link field demands with scientific studies. In this review, we intend to discuss the current status of porcine AI, pointing out challenges and opportunities to improve reproductive efficiency.