bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Metformin Hydrochloride Floating Drug Delivery System: In vitro Study and In vivo Prediction
Authors: Pawar Rajesh , Jagdale Swati
Published: August 2021

Aim: This research work was aimed to evaluate Metformin hydrochloride (MH) floating dosage form by In vitro evaluation/In vivo prediction and to evaluate it’s predictability through it’s application during the R&D using Insilico technique in WINONLIN Software. MH was examined as a model drug, which is a biguanide and is an hypoglycemic agent administered orally. The study was aimed to determine the the systemic concentrations of MH using In-vivo prediction.

Study Design: Fabrication and assessment of Metformin hydrochloride floating drug delivery system: In Vitro evaluation /In Vivo prediction. Biorelevant media was selected for dissolution profile of 12 units of dosage form. Software assisted program used for data feeding and results output.

Methodology: The absorption window for MH is the upper portion of the small gut in which the GI absorption is complete after 6 h. Hence gastroretentive formulation was developed and validity of dissolution study was extended by In vivo pharmacokinetic prediction using WinNonlin Software. A mechanistic oral absorption model was built in Phoenix WinNonlin® software.

In the presented work, significant yet crucial, gastrointestinal (GI) variables are considered for biopredictive dissolution testing to account for a valuable input for physiologically-based pharmacokinetic (PBPK) platform programs. While simulations are performed and mechanistic insights are gained from such simulations from the WinNonlin program.

Results: These floating tablets were observed for In vitro release and studied for In vivo pharmacokinetic prediction. From the obtained values, a meaningful In vivo prediction was done. interestingly from the results attained floating tablets showed sustained drug release and extended drug absorbed in 24h. Fascinatingly, from the data it was proved that drug formulation resides for desired time. The absorption of MH from the developed CR tablet was 1.4 fold higher than its marketed tablet and it had higher AUC0–t values than the marketed product which indicates superior bioavailability of test product compared to marketed tablet with similar dose in Invivo pharmacokinetic prediction. The mean value of biological half-life (t1/2) and Tmax of MH from test formulation is two times more, Test product has shown higher MRT, showing that the drug is maintained longer in the body in comparison to marketed product indicates controlled absorption.

Conclusion: Here we concluded that, a comparative prediction pharmacokinetic evaluation of the fabricated controlled release tablets and the marketed formulation indicates that the fabricated controlled release tablets are well absorbed and the degree of absorption is greater than that of the marketed ER formulation with larger gastric residence time.
Design and Identification of Lead Compounds Targeting Nipah G Attachment Glycoprotein by In Silico Approaches
Authors: James Jainey P. , Apoorva . , Monteiro Shreya Renita , Sukesh K. B. , Varun A.
Published: August 2021

Nipah virus (NiV) caused several outbreaks in Asian countries, including the latest one from the Kerala state of India. There is no drug available against NiV till now, despite its urgent requirement. There are reports about the anti-influenza viral drug Favipiravir, which has positively affected the Nipah virus in vitro models. In the current work, we have provided a computational screening for NiV inhibitors. Twenty-two designed compounds from favipiravir and Nipah glycoprotein, 3D11, were chosen and performed molecular docking to analyse the various conformations and interactions with the amino acids; further, their physicochemical and ADMET properties were also computed. The compound 5_Favipiravir have an excellent docking score (-6.16 kcal/mol), followed by compound 4_Favipiravir and 19_Favipiravir with docking score of -5.50 and -5.38 kcal/mol respectively. The three compounds had the respective heterocyclic moieties such as pyrazole, imidazole and pyrazinone. All the twenty-two designed compounds obey the Lipinski rule of five, which infer that they will not have problems with oral bioavailability.  Thus, it is concluded that the incorporated heterocyclic groups in favipiravir can add to the anti-Nipah activity; hence it can act as future leads for the treatment for the disease caused by Nipah virus.
An Observational Study on Drug Utilization Pattern in Asthma and Chronic Obstructive Pulmonary Disease in Tertiary Care Teaching Hospital
Authors: Hadia Rajesh , Bhatt Priyesha , Panchal Anadisharan , Gandhi Anjali , Rathod Trupal , Joshi Dhaval , Baile Sunil , Maheshwari Rajesh , Ajay Stani , Rajput Hemraj Singh
Published: August 2021

Background: Obstructive airway diseases such as asthma and COPD are defined as a decreased capacity to get air through the conducting airways and out of the lungs.

Objective: To study the drug utilization pattern in asthma and chronic obstructive pulmonary disease, determine irrationally (does not comply with prescription) drug usage, and whether they were prescribed following the standard treatment guidelines.

Methodology: A total of 150 patients of either sex aged 18 years and above having asthma and/or COPD were included in the study. The medical records of patients were checked and information was recorded. The prescriptions were analyzed for drug utilization patterns. The newly diagnosed patients were followed up and medication adherence was determined after 1 month.

Results: Out of all 150 patients there were 103 male and 47 female patients. 54 patients were having asthma, 89 patients COPD, and 7 patients asthma COPD overlap. The majority of the patient were prescribed 1 to 3 drugs per prescription. Inhaled corticosteroids were the highest prescribed drug class. The most commonly prescribed drug combination was budesonide + formoterol. The majority of the patients have poorly adhered to the treatment.

Conclusion: Study data highlights that very few drug interactions were identified between prescribed medications. The drugs and their combinations were prescribed according to the standard guidelines GOLD (Global Initiative for Chronic Obstructive Lung Disease) and GINA (Global Initiative for Asthma).
Role of Anti-VEGF (Bevacizumab) in Management of Neovascular Glaucoma: A Review
Authors: Alharfy Abdulrahman Arshed N. , Albalawi Marwan Saleh D. , Alzahrani Abdulmajeed Mousa , Alsubaie Ruby Naif M. , Albalawi Amani Ahmad S. , Alkaabneh Waad Ali , Altidlawi Abdullah Ibrahim , Alharbi Amal Nafea J. , Almutairi Afnan Mohammed H. , Alotabi Rola Ali S.
Published: August 2021

Neovascular glaucoma (NVG) is an aggressive type of glaucoma, which often results in poor visual outcomes. Antivascular endothelial growth factor is frequently used for various conditions in which VEGF release is induced in response to retinal ischemia. Bevacizumab is a humanized anti-VEGF monoclonal IgG1 antibody. The potential of antivascular endothelial growth factor (anti-VEGF) agents to modify the disease course of neovascular glaucoma (NVG) was recognized shortly after their use in the treatment of age-related macular degeneration was reported. These medications were noted to induce rapid regression of the anterior segment neovascularization that characterizes NVG. Several studies as well as extensive clinical experience have demonstrated a rapid regression of anterior segment neovascularization following the injection of anti-VEGF agents. This review aims to summarize current evidences regarding effectiveness of Bevacizumab in management of neovascular glaucoma.
Health Research Conducting Quality Perceptions of Medical Postgraduate Trainees
Authors: Chouhan Shanti , Memon Khalida Naz
Published: August 2021

Background: Health researchers in medical universities are surrounded by existing hurdles to the health research during the process of conduction which may affect the quality of conduction of health research undertaken by the medical trainees. The current study is conducted to determine the effects of barriers on the quality of conduction of health research.

Study Design: Descriptive cross-sectional study.

Place and Duration of Study: Research conducting postgraduate trainees in various disciplines in Liaqaut University of Medical & Health Sciences, Jamshoro from 1st September 2018 to 31st December 2018.

Methodology: Two hundred & sixteen health research trainees were recruited for study                    through stratified sampling technique; the subjects included 79 males &137 females of age bracket of 24-50 years. After taking the consent, data was collected on a preformed questionnaire and analyzed in SPSS version 23.0 by computing proportions, mean ± standard deviation and using Chi-square test as statistical test of significance with the p-value of 0.05 taken as level of significance.

Results: Overall, two hundred and fifty subjects were approached to obtain the complete response of the required sample of two hundred and sixteen. The response rate was 86.4%. The 72 (33.3%) trainees in medicine and allied sciences, 66 (92%) trainees experienced various barriers in quality of conducting of health research. From 42 (19.4%) trainees in surgery and allied sciences, 22 (51.2%) perceived effects of barriers on their health research conducting (HRC) quality. Amongst 33 (15.3%) trainees in basic sciences, 15 (45%) faced various hurdles while going through their research; surprisingly all the trainees conducting research in field of pharmacology faced various barriers during research process. Out of 67 (31.0%) postgraduate trainees in dentistry, 60 (90%) reported various barriers (p= 0.03).

Conclusion: Quality conduction of health research affected by barriers is experienced by majority of medical researchers and trainees during their postgraduate training.  The majority of the postgraduate trainees conducting research from clinical fields face more effects on their research conducting quality as compared to the basic sciences researchers.

Recommendation: Quality assessment protocol should be incorporated during research conducting process. Actions should be taken for reducing the barriers related to HRC quality. Collaborative health research amongst clinical and basic sciences fields can be done to improve the quality.
Changes in Body Weight and Knee Pain in Adults With Knee Osteoarthritis Three‐and‐a‐Half Years After Completing Diet and Exercise Interventions: Follow‐Up Study for a Single‐Blind, Single‐Center, Randomized Controlled Trial
Authors: Messier Stephen P. , Newman Jovita J. , Scarlett Matthew J. , Mihalko Shannon L. , Miller Gary D. , Nicklas Barbara J. , DeVita Paul , Hunter David J. , Lyles Mary F. , Eckstein Felix , Guermazi Ali , Loeser Richard F. , Beavers Daniel P.
Published: August 2021

Objective

To determine whether long‐term diet (D) and exercise (E) interventions, alone or in combination (D+E), have beneficial effects for older adults with knee osteoarthritis (OA) 3.5 years after the interventions end.

Methods

This is a secondary analysis of a subset (n = 94) of the first 184 participants who had successfully completed the Intensive Diet and Exercise in Arthritis (IDEA) trial (n = 399) and who consented to follow‐up testing. Participants were older (age ≥55 years), overweight, and obese adults with radiographic and symptomatic knee OA in at least 1 knee who completed 1.5‐year D+E (n = 27), D (n = 35), or E (n = 32) interventions and returned for 5‐year follow‐up testing an average of 3.5 years later.

Results

During the 3.5‐years following the interventions, weight regain in D+E and D was 5.9 kg (7%) and 3.1 kg (4%), respectively, with a 1‐kg (1%) weight loss in E. Compared to baseline, weight (D+E –3.7 kg [P = 0.0007], D –5.8 kg [P < 0.0001], E –2.9 kg [P = 0.003]) and Western Ontario and McMaster Universities Osteoarthritis Index pain subscale scores (D+E –1.2 [P = 0.03], D –1.5 [P = 0.001], E –1.6 [P = 0.0008]) were lower in each group at the 5‐year follow‐up. The effect of group assignment at the 5‐year follow‐up was significant for body weight, with D being less than E (–3.5 kg; P = 0.04).

Conclusion

Older adults with knee OA who completed 1.5‐year D or D+E interventions experienced partial weight regain 3.5 years later; yet, relative to baseline, they preserved statistically significant changes in weight loss and reductions in knee pain.
Polypharmacy and Potentially Inappropriate Medication Use in Older Adults With Systemic Lupus Erythematosus
Authors: Séguin Dale Jean‐Guy , Peschken Christine A. , Dolovich Cassandra , Grymonpre Ruby E. , St. John Philip D. , Tisseverasinghe Annaliese
Published: August 2021

Objective

To assess the prevalence and potential risk factors for polypharmacy and prescribing of the potentially inappropriate medications, opioids and benzodiazepines/Z‐drugs, in older adults with systemic lupus erythematosus (SLE).

Methods

The study population comprised adults age ≥50 years meeting American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria followed at a tertiary care rheumatology clinic. Information on prescriptions filled in the 4 months preceding chart review was obtained from the Manitoba Drug Program Information Network. Clinical data, including age, sex, Charlson Comorbidity Index (CCI) score, Systemic Lupus Erythematosus Disease Activity Index 2000 score, prednisone use, SLE duration, and rural residence were abstracted from electronic medical records. Logistic regression analyses were performed to assess any association between polypharmacy (using 2 definitions: ≥5 and ≥10 medications), potentially inappropriate medication use, and clinical features.

Results

A total of 206 patients (mean age 62 years, 91% female, 36% rural) were included: 148 (72%) filled ≥5 medications, 71 (35%) filled ≥10 medications, 63 (31%) used benzodiazepines/Z‐drugs, and 50 (24%) used opioids. Among the 77 patients age ≥65 years, 57 (74%) filled ≥5 medications, and 26 (34%) filled ≥10 medications, compared to 30% and 4%, respectively, of Manitobans age ≥65 years (National Prescription Drug Utilization Information System, 2016). The odds of polypharmacy were greater with prednisone use (adjusted odds ratio [OR] 3.70 [95% confidence interval (95% CI) 1.40–9.79] for ≥5 medications), CCI score (adjusted OR 1.62 [95% CI 1.20–2.17]), and rural residence (adjusted OR 2.05 [95% CI 1.01–4.18]). Odds of benzodiazepine/Z‐drug use were increased with polypharmacy (adjusted OR 4.35 [95% CI 1.69–11.22]), and odds of opioid use were increased with polypharmacy (adjusted OR 6.75 [95% CI 1.93–23.69]) and CCI score (adjusted OR 1.29 [95% CI 1.08–1.54]).

Conclusion

The prevalence of polypharmacy in this SLE cohort was higher than in the general Manitoban population. Polypharmacy is a strong marker for use of prescription benzodiazepines/Z‐drugs and opioids.
2D Titanium Carbide (MXene) Based Films: Expanding the Frontier of Functional Film Materials
Authors: Li Guohao , Wyatt Brian C. , Song Fei , Yu Changqiang , Wu Zhenjun , Xie Xiuqiang , Anasori Babak , Zhang Nan
Published: August 2021

2D titanium carbide (Ti3C2Tx) MXene films, with their well‐defined microstructures and chemical functionality, provide a macroscale use of nano‐sized Ti3C2Tx flakes. Ti3C2Tx films have attractive physicochemical properties favorable for device design, such as high electrical conductivity (up to 20 000 S cm–1), impressive volumetric capacitance (1500 F cm–3), strong in‐plane mechanical strength (up to 570 MPa), and a high degree of flexibility. Here, the appealing features of Ti3C2Tx‐based films enabled by the layer‐to‐layer arrangement of nanosheets are reviewed. We devote attention to the key strategies for actualizing desirable characteristics in Ti3C2Tx‐based functional films, such as high and tunable electrical conductivity, outstanding mechanical properties, enhanced oxidation‐resistance and shelf life, hydrophilicity/hydrophobicity, adjustable porosity, and convenient processability. This review further discusses fundamental aspects and advances in the applications of Ti3C2Tx‐based films with a focus on illuminating the relationship between the structural features and the resulting performances for target applications. Finally, the challenges and opportunities in terms of future research, development, and applications of Ti3C2Tx‐based films are suggested. A comprehensive understanding of these competitive features and challenges shall provide guidelines and inspiration for the further development of Ti3C2Tx‐based functional films, and contribute to the advances in MXene technology.
Plasmonically Enhanced CRISPR/Cas13a‐Based Bioassay for Amplification‐Free Detection of Cancer‐Associated RNA
Authors: Liu Lin , Wang Zheyu , Wang Yixuan , Luan Jingyi , Morrissey Jeremiah J. , Naik Rajesh R. , Singamaneni Srikanth
Published: August 2021

Novel methods that enable sensitive, accurate and rapid detection of RNA would not only benefit fundamental biological studies but also serve as diagnostic tools for various pathological conditions, including bacterial and viral infections and cancer. Although highly sensitive, existing methods for RNA detection involve long turn‐around time and extensive capital equipment. Here, an ultrasensitive and amplification‐free RNA quantification method is demonstrated by integrating CRISPR‐Cas13a system with an ultrabright fluorescent nanolabel, plasmonic fluor. This plasmonically enhanced CRISPR‐powered assay exhibits nearly 1000‐fold lower limit‐of‐detection compared to conventional assay relying on enzymatic reporters. Using a xenograft tumor mouse model, it is demonstrated that this novel bioassay can be used for ultrasensitive and quantitative monitoring of cancer biomarker (lncRNA H19). The novel biodetection approach described here provides a rapid, ultrasensitive, and amplification‐free strategy that can be broadly employed for detection of various RNA biomarkers, even in resource‐limited settings.
Homogeneous Carbon/Potassium‐Incorporation Strategy for Synthesizing Red Polymeric Carbon Nitride Capable of Near‐Infrared Photocatalytic H2 Production
Authors: Xu Yangsen , Fan Mingjian , Yang Wenjuan , Xiao Yonghao , Zeng Lingting , Wu Xiao , Xu Qinghua , Su Chenliang , He Qianjun
Published: August 2021

The efficient utilization of near‐infrared (NIR) light for photocatalytic hydrogen generation is vitally important to both solar hydrogen energy and hydrogen medicine, but remains a challenge at present, owing to the strict requirement of the semiconductor for high NIR responsiveness, narrow bandgap, and suitable redox potentials. Here, an NIR‐active carbon/potassium‐doped red polymeric carbon nitride (RPCN) is achieved for by using a similar‐structure dopant as the melamine (C3H6N6) precursor with the solid KCl. The homogeneous and high incorporation of carbon and potassium remarkably narrows the bandgap of carbon nitride (1.7 eV) and endows RPCN with a high NIR‐photocatalytic activity for H2 evolution from water at the rate of 140 µmol h−1 g−1 under NIR irradiation (700 nm ≤ λ ≤ 780 nm), and the apparent quantum efficiency is high as 0.84% at 700 ± 10 nm (and 13% at 500 ± 10 nm). A proof‐of‐concept experiment on a tumor‐bearing mouse model verifies RPCN as being capable of intratumoral NIR‐photocatalytic hydrogen generation and simultaneous glutathione deprivation for safe and high‐efficacy drug‐free cancer therapy. The results shed light on designing efficient photocatalysts to capture the full spectrum of solar energy, and also pioneer a new pathway to develop NIR photocatalysts for hydrogen therapy of major diseases.
Switching Reactive Oxygen Species into Reactive Nitrogen Species by Photocleaved O2‐Released Nanoplatforms Favors Hypoxic Tumor Repression
Authors: Luo Tao , Wang Duo , Liu Lidong , Zhang Yan , Han Chuangye , Xie Ying , Liu Yan , Liang Jingchen , Qiu Guanhua , Li Hongxue , Su Danke , Liu Junjie , Zhang Kun
Published: August 2021

In various reactive oxygen species (ROS)‐based antitumor approaches (e.g., photodynamic therapy), increasing attentions are made to improve ROS level, but the short lifetime that is another decisive hurdle of ROS‐based antitumor outcomes is not even explored yet. To address it, a photocleaved O2‐released nanoplatform is constructed to release and switch ROS into reactive nitrogen species (RNS) for repressing hypoxic breast tumor. Systematic explorations validate that the nanoplatforms can attain continuous photocontrolled O2 release, alleviate hypoxia, and elevate ROS level. More significantly, the entrapped PDE5 inhibitor (PDE5‐i) in this nanoplatform can be enzymatically decomposed into nitric oxide that further combines with ROS to generate RNS, enabling the persistent antitumor effect since RNS features longer lifetime than ROS. Intriguingly, ROS conversion into RNS can help ROS to evade the hypoxia‐induced resistance to ROS‐based antitumor. Eventually, RNS production unlocks robust antitumor performances along with ROS elevation and hypoxia mitigation. Moreover, this extraordinary conversion from ROS into RNS also can act as a general method to solve the short lifetime of ROS.
Multiscale Understanding of Covalently Fixed Sulfur–Polyacrylonitrile Composite as Advanced Cathode for Metal–Sulfur Batteries
Authors: Ahmed Mohammad Shamsuddin , Lee Suyeong , Agostini Marco , Jeong Min‐Gi , Jung Hun‐Gi , Ming Jun , Sun Yang‐Kook , Kim Jaekook , Hwang Jang‐Yeon
Published: August 2021

Metal–sulfur batteries (MSBs) provide high specific capacity due to the reversible redox mechanism based on conversion reaction that makes this battery a more promising candidate for next‐generation energy storage systems. Recently, along with elemental sulfur (S8), sulfurized polyacrylonitrile (SPAN), in which active sulfur moieties are covalently bounded to carbon backbone, has received significant attention as an electrode material. Importantly, SPAN can serve as a universal cathode with minimized metal–polysulfide dissolution because sulfur is immobilized through covalent bonding at the carbon backbone. Considering these unique structural features, SPAN represents a new approach beyond elemental S8 for MSBs. However, the development of SPAN electrodes is in its infancy stage compared to conventional S8 cathodes because several issues such as chemical structure, attached sulfur chain lengths, and over‐capacity in the first cycle remain unresolved. In addition, physical, chemical, or specific treatments are required for tuning intrinsic properties such as sulfur loading, porosity, and conductivity, which have a pivotal role in improving battery performance. This review discusses the fundamental and technological discussions on SPAN synthesis, physicochemical properties, and electrochemical performance in MSBs. Further, the essential guidance will provide research directions on SPAN electrodes for potential and industrial applications of MSBs.
Surface Phosphorus‐Induced CoO Coupling to Monolithic Carbon for Efficient Air Electrode of Quasi‐Solid‐State Zn–Air Batteries
Authors: Liu Huan , Liu Yanyan , Mehdi Sehrish , Wu Xianli , Liu Tao , Zhou Benji , Zhang Pengxiang , Jiang Jianchun , Li Baojun
Published: August 2021

One challenge facing the development of air electrodes for Zn–air batteries (ZABs) is the embedment of active sites into carbon, which requires cracks and blends between powder and membrane and results in low energy efficiency during manufacturing and utilization. Herein, a surface phosphorization‐monolithic strategy is proposed to embed CoO nanoparticles into paulownia carbon plate (P–CoO@PWC) as monolithic electrodes. Benefiting from the retention of natural transport channels, P–CoO@PWC‐2 is conducive to the construction of three‐phase interface structure for efficient mass transfer and high electrical conductivity. The electrode exhibits remarkable catalytic activities for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) with a small overpotential gap (EOER − EORR = 0.68 V). Density functional theory calculations reveal that the incorporation of P on P–CoO@PWC‐2 surface adjusts the electronic structure to promote the dissociation of water and the activation of oxygen, thus inducing catalytic activity. The monolithic P–CoO@PWC‐2 electrode for quasi‐solid‐state or aqueous ZABs has excellent specific power, low charge–discharge voltage gap (0.83 V), and long‐term cycling stability (over 700 cycles). This work serves as a new avenue for transforming abundant biomass into high‐value energy‐related engineering products.
Toward Sustainable, Colorless, and Transparent Photovoltaics: State of the Art and Perspectives for the Development of Selective Near‐Infrared Dye‐Sensitized Solar Cells
Authors: Grifoni Fionnuala , Bonomo Matteo , Naim Waad , Barbero Nadia , Alnasser Thomas , Dzeba Iva , Giordano Marco , Tsaturyan Arshak , Urbani Maxence , Torres Tomas , Barolo Claudia , Sauvage Frédéric
Published: August 2021

Dye‐sensitized solar cell (DSSC) is one of the promising photovoltaic (PV) technologies for applications requiring high aesthetic features combined with energy production such as building integration PV (BIPV). In this context, DSSCs have the ability to be wavelength selective, thanks to the development of new sensitizers by molecular engineering. The long history of dye research has afforded is technology different colorations for reaching panchromatic light absorption. However, nearly 45% of radiation from sunlight lies in the near‐infrared (NIR) region, where human cones are not sensitive. This review provides the reader with key information on how to selectively exploit this region to develop colorless and transparent PV based on DSSC technology. Besides selective NIR absorbers, the triptych photoanode, counter‐electrode, and redox mediator are together contributing to reach high aesthetic features. Details of all the components, interplay, and an opinion on the technological limitations to reach colorless and transparent NIR‐DSSC are herein discussed in relationship with BIPV applications.
Stable and Dendrite‐Free Lithium Metal Anodes Enabled by Ionic/Electronic Li2S/Mo Interlayer
Authors: Fan Lishuang , Guo Zhikun , Zhao Dan , Zhao Chenyang , Lu Xingyuan , Chen Aosai , Yin Xiaoju , Zhang Yu , Sun Bing , Zhang Naiqing
Published: August 2021

The wide applications of high‐capacity lithium metal anodes for lithium metal batteries are restricted by the uncontrollable lithium dendrite growth caused by the uneven lithium deposition and the infinite volume change of lithium anodes during the plating/stripping process. Herein, the composite ionic/electronic interlayer of Li2S/Mo is deposited on the surface of stainless steel mesh (SSM) by in situ electrochemical conversion reaction from MoS2 nanosheet arrays. The Li2S/Mo interlayer with high ionic conductivity can regulate uniform lithium‐ion flux and promote homogeneous lithium deposition without dendrite growth. The half cells with Li2S/Mo‐modified SSM current collector show stable cycling performance of more than 400 cycles at 1 and 1 mAh cm−2, with the average Coulombic efficiency higher than 96%. By coupling with LiFePO4 cathodes, the assembled full cells demonstrate improved cycling performance. This work provides a new idea for using metal sulfides as a lithiophilic interlayer to facilitate dendrite‐free lithium deposition.
Neuroimaging in Kabuki syndrome and another KMT2D‐related disorder
Authors: Stadelmaier Rachel T. , Kenna Margaret A. , Barrett Devon , Mullen Thomas E. , Bodamer Olaf , Agrawal Pankaj B. , Robson Caroline D. , Wojcik Monica H.
Published: August 2021

Recognition of distinct phenotypic features is an important component of genetic diagnosis. Although CHARGE syndrome, Kabuki syndrome, and a recently delineated KMT2D Ex 38/39 allelic disorder exhibit significant overlap, differences on neuroimaging may help distinguish these conditions and guide genetic testing and variant interpretation. We present an infant clinically diagnosed with CHARGE syndrome but subsequently found to have a de novo missense variant in exon 38 of KMT2D, the gene implicated in both Kabuki syndrome and a distinct KMT2D allelic disorder. We compare her brain and inner ear morphology to a retrospective cohort of 21 patients with classic Kabuki syndrome and to typical CHARGE syndrome findings described in the literature. Thirteen of the 21 Kabuki syndrome patients had temporal bone imaging (5/13 CT, 12/13 MRI) and/or brain MRI (12/13) which revealed findings distinct from both CHARGE syndrome and the KMT2D allelic disorder. Our findings further elucidate the spectrum of inner ear dysmorphology distinguishing Kabuki syndrome and the KMT2D allelic disorder from CHARGE syndrome, suggesting that these three disorders may be differentiated at least in part by their inner ear anomalies.
Truce–Smiles Rearrangements by Strain Release: Harnessing Primary Alkyl Radicals for Metal‐Free Arylation
Authors: Whalley David M. , Seayad Jayasree , Greaney Michael F.
Published: August 2021

The ring‐opening of 3‐aminocyclobutanone oximes enables easy generation of primary alkyl radicals, capable of undergoing an unprecedented strain‐release, desulfonylative radical Truce–Smiles rearrangement, providing divergent access to valuable 1,3 diamines and unnatural β‐amino acids. Characterized by mild conditions and wide scope of migrating species, this protocol allows the modular assembly of sp3‐aryls under transition metal‐free, room‐temperature conditions.
Double Double to Double Perovskite Transformations in Quaternary Manganese Oxides
Authors: Ji Kunlang , Alharbi Khalid N. , Solana‐Madruga Elena , Moyo Gessica T. , Ritter Clemens , Attfield J. Paul
Published: August 2021

Control of cation ordering in ABX3 perovskites is important to structural, physical and chemical properties. Here we show that thermal transformations of AA′BB′O6 double double perovskites, where both A and B sites have 1:1 cation order, to (A0.5A′0.5)2BB′O6 double perovskites with fully disordered A/A′ cations can be achieved under pressure in CaMnMnWO6 and SmMnMnTaO6, enabling both polymorphs of each material to be recovered. This leads to a dramatic switch of magnetic properties from ferrimagnetic order in double double perovskite CaMnMnWO6 to spin glass behaviour in the highly frustrated double perovskite polymorph. Comparison of double double and double perovskite polymorphs of other materials will enable effects of cation order and disorder on other properties such as ferroelectricity and conductivity to be explored.
13C‐Labeled Diethyl Ketoglutarate Derivatives as Hyperpolarized Probes of 2‐Ketoglutarate Dehydrogenase Activity
Authors: Singh Jaspal , Suh Eul Hyun , Sharma Gaurav , Chen Jun , Hackett Edward P. , Wen Xiaodong , Sherry A. Dean , Khemtong Chalermchai , Malloy Craig R. , Park Jae Mo , Kovacs Zoltan
Published: August 2021

The TCA cycle is a central metabolic pathway for energy production and biosynthesis. A major control point of metabolic flux through the cycle is the decarboxylation of 2‐ketoglutarate by the TCA cycle enzyme 2‐ketoglutarate dehydrogenase (2‐KGDH). In this project, we developed 13C labeled 2‐ketoglutarate derivatives to monitor 2‐KGDH activity in vivo. 13C NMR analysis of liver extracts revealed that uniformly 13C labeled 2‐ketogutarate, in its cell permeable ester form, was rapidly taken up and hydrolyzed in liver and underwent extensive metabolism to produce labeled glutamate, succinate, lactate and other metabolites. Diethyl [1,2‐13C2]‐2‐ketoglutarate was successfully polarized by dynamic nuclear polarization and within seconds after injection into rats, the probe produced hyperpolarized [13C]bicarbonate in the liver reflecting flux through the TCA cycle. These experiments demonstrate that this tracer offers the possibility of directly monitoring flux through 2‐KGDH in vivo.
The role of peri‐device leak closure after left atrial appendage occlusion: A safe and feasible approach
Authors: Musumeci Giuseppe , Civera Stefania
Published: August 2021

Key Points

Peri‐device leak (PDL) after left atrial appendage (LAA) occlusion may hamper the safe discontinuation of oral anticoagulation.

PDL closure with either endovascular coils, plugs or second occluders is a safe and feasible alternative.

Further randomized trial are needed in order to establish clinical efficacy in stroke risk reduction.
Targeted Protein Depletion Using the Auxin‐Inducible Degron 2 (AID2) System
Authors: Saito Yuichiro , Kanemaki Masato T.
Published: August 2021

Targeted protein depletion using a conditional degron is a powerful method to probe the role of proteins in living cells because of the speed with which depletion can be induced and its reversibility. The auxin‐inducible degron (AID) is one of the most common degron‐based technologies used in cell biology. We recently established an improved system, called AID2, which involves expressing a mutant E3 ligase subunit, OsTIR1(F74G), and fusing a protein of interest to the mini‐AID (mAID) tag, and that employs a new and more potent ligand, 5‐phenyl‐indole‐3‐acetic acid (5‐Ph‐IAA). The AID2 system overcomes some of the drawbacks associated with the original AID system, i.e., leaky degradation without auxin and the requirement of high auxin doses. With AID2 it is, therefore, now possible to control a degron‐fused protein more precisely, enabling target proteins to be degraded with a half‐life of 10 to 45 min via the addition of a low dose of 5‐Ph‐IAA. Importantly, in AID2, it is not necessary to control the expression of OsTIR1(F74G) for suppressing leaky degradation and a parental cell line constitutively expressing OsTIR1(F74G) can be used for the generation of multiple mAID‐tagged proteins. Here, we describe a protocol for the tagging of endogenous proteins with mAID in diploid HCT116 cells. Our protocol can be applied to other mammalian cell lines and will enhance the utility of AID2 for studying protein functions in living cells. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Generation of a parental HCT116 cell line expressing OsTIR1(F74G)

Basic Protocol 2: Construction of CRISPR and donor plasmids for tagging endogenous genes

Basic Protocol 3: Generation of cell lines expressing a protein of interest fused with mAID
What is it about coral reefs? Translation of ecosystem goods and services relevant to people and their well‐being
Authors: Santavy Deborah L. , Horstmann Christina L. , Sharpe Leah M. , Yee Susan H. , Ringold Paul
Published: August 2021

There is an astonishing diversity of ways in which people benefit from coral reefs. They provide recreation, resource extraction, inspirational, and educational opportunities, among many others as well as being valued just for their existence. As the condition of coral reef ecosystems decline, so do their ability to provide these benefits. Prudent management of coral reefs and the benefits they provide are important as some predict most coral reefs globally will be lost by the mid‐21st century. Meanwhile, coral reef managers have limited tools and relevant data to design and implement effective environmental management practices that will enable coral reefs to provide benefits demanded by society. We demonstrate an approach to identify and measure environmental components of coral reefs that directly benefit human well‐being. The approach views ecosystems through the lens of a specific set of beneficiaries and the biophysical features directly relevant to each. We call these biophysical features Final Ecosystem Goods and Services (FEGS). In our demonstration, we (1) identify a range of beneficiaries of coral reefs; (2) identify metrics of FEGS for those beneficiaries; and (3) describe how data quantifying those biophysical metrics might be used to facilitate greater economic and social understanding.
Saltwater and phosphorus drive unique soil biogeochemical processes in freshwater and brackish wetland mesocosms
Authors: Servais Shelby , Kominoski John S. , Fernandez Marco , Morales Kristina
Published: August 2021

Coastal ecosystems are exposed to saltwater intrusion but differential effects on biogeochemical cycling are uncertain. We tested how elevated salinity and phosphorus (P) individually and interactively affect microbial activities and biogeochemical cycling in freshwater and brackish wetland soils. In experimental mesocosms, we added crossed gradients of elevated concentrations of soluble reactive P (SRP) (0, 20, 40, 60, 80 μg/L) and salinity (0, 4, 7, 12, 16 ppt) to freshwater and brackish peat soils (10, 14, 17, 22, 26 ppt) for 35 d. We quantified changes in water chemistry [dissolved organic carbon (DOC), ammonium (), nitrate + nitrite (N + N), SRP concentrations], soil microbial extracellular enzyme activities, respiration rates, microbial biomass C, and soil chemistry (%C, %N, %P, C:N, C:P, N:P). DOC, , and SRP increased in freshwater but decreased in brackish mesocosms with elevated salinity. DOC similarly decreased in brackish mesocosms with added P, and N + N decreased with elevated salinity in both freshwater and brackish mesocosms. In freshwater soils, water column P uptake occurred only in the absence of elevated salinity and when P was above 40 µg/L. Freshwater microbial EEAs, respiration rates, and microbial biomass C were consistently higher compared to those from brackish soils, and soil phosphatase activities and microbial respiration rates in freshwater soils decreased with elevated salinity. Elevated salinity increased arylsulfatase activities and microbial biomass C in brackish soils, and elevated P increased microbial respiration rates in brackish soils. Freshwater soil %C, %N, %P decreased and C:P and N:P increased with elevated salinity. Elevated P increased %C and C:N in freshwater soils and increased %P but decreased C:P and N:P in brackish soils. Freshwater soils released more C and nutrients than brackish soils when exposed to elevated salinity, and both soils were less responsive to elevated P than expected. Freshwater soils became more nutrient‐depleted with elevated salinity, whereas brackish soils were unaffected by salinity but increased P uptake. Microbial activities in freshwater soils were inhibited by elevated salinity and unaffected by added P, but brackish soil microbial activities slightly increased with elevated salinity and P.
Acetylcholinesterase Biosensor Based on Reduced Graphene Oxide – Carbon Black Composite for Determination of Reversible Inhibitors
Authors: Shamagsumova R. , Rogov A. , Shurpik D. , Stoikov I. , Evtugyn G.
Published: August 2021

For the first time, acetylcholinesterase (AChE) biosensors based on mixed carbon nanomaterials (electrochemically reduced graphene oxide (ERGO) and carbon black (CB) particles) were described for the determination of antidementia drugs. Changes in the content of underlying layer allowed varying selectivity and sensitivity of the inhibitor determination. Appropriate limits of detection (LOD) varied in the range from 1 pM to 0.1 nM for donepezil, 5 nM–0.1 μM for berberine, 0.1–50 nM for huperzine A and 0.1–300 nM for galantamine. Variation in the inhibition measurement parameters can be used for increasing selectivity of the measurements.
Invaders for sale: the ongoing spread of invasive species by the plant trade industry
Authors: Beaury Evelyn M , Patrick Madeline , Bradley Bethany A
Published: August 2021

The sale of ornamental nonnative plants is a primary pathway of invasive plant introduction into the US. As a result, many nonnative plants have been identified as noxious weeds by federal and state governments, or as problematic invasive plants by agencies and nonprofit organizations. However, it is unclear whether identifying a species as invasive has curtailed its sale as an ornamental. Using the Google search engine and a database of nursery catalogs, we found that 61% of 1285 plant species identified as invasive in the US remain available through the plant trade, including 50% of state‐regulated species and 20% of federal noxious weeds. Vendors offering invasive plants were located in all lower 48 states. The widespread availability of invasive plants in the US is likely a symptom of disjointed state regulations that fail to protect ecosystems and economies. Regional regulation coupled with outreach to growers and consumers is needed to reduce the ongoing propagation of invasive plants in the US.
Intravascular imaging–guided intracoronary lithotripsy: First real‐world experience
Authors: Sinclair Hannah , Fan Lampson , Fahy Eoin , Shahid Farhan , Ratib Karim , Nolan James , Mamas Mamas , Zaman Azfar , Ahmed Javed
Published: August 2021

Background and Aims

Coronary calcification remains a significant challenge for the contemporary interventional cardiologist. We aim to describe the use of intravascular lithotripsy (IVL) in a range of real‐world settings.

Methods

A retrospective two‐center analysis of patients treated with IVL between June 2018 and November 2019. Technical and procedural success, as well as procedural complications and 30‐day outcomes (death, myocardial infarction, or repeat target vessel revascularization), was recorded.

Results

Sixty‐five patients underwent IVL: 80% were male and the mean age was 70.1 ± 12.0 years. 54% of patients presented with acute coronary syndrome (ACS) and 68% of patients had intracoronary imaging. Twelve patients required IVL within pre‐existing stents, and 12 underwent IVL in the left main stem. All balloons were successfully delivered with 98.5% procedural success. There was a significant gain in MLA post PCI of 261.9 ± 100% following IVL. There were two procedural complications. At 30‐day follow‐up, there was one death, and one patient required a repeat procedure due to stent underexpansion.

Conclusions

In this largest real‐world series of imaging‐guided IVL for calcified lesions to date, we demonstrate that IVL is deliverable, safe, and effective at calcium modification especially when intracoronary imaging is used.
Preparation and characterization of silk fibroin/polyethylene oxide nanofiber membranes with antibacterial activity
Authors: Lan Dongwei , Liu Zulan , Zhou Jiale , Xu Mengting , Li Zhi , Dai Fangyin
Published: August 2021

Bacterial infection is among the most common diseases that threaten human health. Antibiotics are effective in treating bacterial infections. However, the overuse of antibiotics will lead to an increase in bacterial resistance. To reduce the overuse of antibiotics and improve the effective use of antibiotics through slow release, silk fibroin (SF)/polyethylene oxide (PEO) nanofiber membranes with different SF and PEO proportions were prepared by electrospinning. The ecofriendly solvent ethanol solution was used for electrospinning for better protection of antibiotic activity. The SEM showed that the surface of SF/PEO (2:8) and SF/PEO (3:7) was smoother and more uniform. With the increase of SF content, the thermal stability and hydrophilicity of SF/PEO nanofiber membranes were improved. The SF/PEO (3:7) nanofiber membrane had the best mechanical property and its maximum stress and strain were 4.6 1 ± 0.24 MPa and 16.36 ± 0.41%, respectively. Based on these good properties, SF/PEO (3:7) nanofiber membrane was chosen for loading and releasing gentamicin sulfate (GS). The fabricated (GS)/SF/PEO (3:7) nanofiber membrane exhibited good release efficiency and showed the good antibacterial activity against Staphylococcus aureus and Escherichia coli. These investigations indicated the GS/SF/PEO (3:7) nanofiber membrane (GS/SF/PEO) has a great potential for application in antibacterial materials.
Downregulation of long noncoding RNA SNHG7 protects against inflammation and apoptosis in Parkinson's disease model by targeting the miR‐425‐5p/TRAF5/NF‐κB axis
Authors: Zhang Haiquan , Wang Zhiyong , Hu Keqi , Liu Handong
Published: August 2021

Accumulated evidence has manifested that long noncoding RNA (lncRNA) is involved in the progress of Parkinson's disease (PD). SNHG7, a novel lncRNA, has been found to be involved in tumorigenesis. However, SNHG7 expression and its functional effects on PD remain uncharted. Rotenone (Rot) was adopted to construct PD models in Sprague‐Dawley (SD) rats and SH‐SY5Y cells, respectively. The expression levels of caspase 3, tyrosine hydroxylase (TH), ionized calcium‐binding adapter molecule 1 (Iba1) in SD rat striatum were measured via immunohistochemistry and western blot. Additionally, the expressions of inflammatory cytokines (interleukin 1β [IL‐1β], IL‐6, tumor necrosis factor α) and oxidative stress factors (malondialdehyde, superoxide dismutase, and glutathione peroxidase) in the brain tissues were examined using real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay, respectively. Moreover, the protein levels of tumor necrosis factor receptor‐associated factor (TRAF5), I‐κB, nuclear factor‐κB (NF‐κB), HO‐1, Nrf2 were detected via western blot. Bioinformatics was applied to predict the targeting relationship between SNHG7, miR‐425‐5p, and TRAF5. Dual‐luciferase activity assay and RNA immunoprecipitation assays were conducted to verify their interactions. In comparison to healthy donors, SNHG7 was found upregulated while miR‐425‐5p expression was downregulated in PD patients. Functional experiments confirmed that SNHG7 downregulation or miR‐425‐5p overexpression attenuated neuronal apoptosis in the Rot‐mediated PD model, TH‐positive cell loss, and microglial activation by mitigating inflammation and oxidative stress. Mechanistically, SNHG7 served as a competitive endogenous RNA by sponging miR‐425‐5p and promoted TRAF5 mediated inflammation and oxidative stress. Inhibition of SNHG7 ameliorated neuronal apoptosis in PD through relieving miR‐425‐5p/TRAF5/NF‐κB signaling pathway modulated inflammation and oxidative stress, and similar results were observed in the Rot‐mediated rat model of PD.
The impact of cryopreservation in signature markers and immunomodulatory profile of tendon and ligament derived cells
Authors: Gonçalves Ana I. , Vinhas Adriana , Rodrigues Márcia T. , Gomes Manuela E.
Published: August 2021

Tendon and ligament (T/L) engineering strategies towards clinical practice have been challenged by a paucity of understanding in the identification and still poorly described characterization of cellular niches. Prospecting how resident cell populations behave in vitro, and how cryopreservation may influence T/
L‐promoting factors, can provide insights into T/
L‐cellular profiles for novel regenerative solutions. Therefore, we studied human T/
L‐derived cells isolated from patellar tendons and cruciate ligaments as suitable cellular models to anticipate tendon and ligament niches responses for advanced strategies with predictive tenogenic and ligamentogenic value. Our results show that the crude populations isolated from tendon and ligament tissues hold a stem cell subset and share a similar behavior in terms of tenogenic/ligamentogenic commitment. Both T/
L‐derived cells successfully undergo cryopreservation/thawing maintaining the tenogenic/ligamentogenic profiles. The major differences between cryopreserved and fresh populations were observed at the gene expression of MKX, SCX, and TNMD as well as at the protein levels of collagen type I and III, in which cells from tendon origin (hTDCs) evidence increased values in comparison to the ones from ligament (hLDCs, p < 0.05). In addition, low‐temperature storage was shown to potentiate an immunomodulatory profile of cells, especially in hTDCs leading to an increase in the gene expression of the anti‐inflammatory factors IL‐4 and IL‐10 (p < 0.05), as well as in the protein secretion of IL‐10 (p < 0.01) and IL‐4 (p < 0.001). Overall, the outcomes highlight the relevance of the cryopreserved T/
L‐derived cells and their promising immunomodulatory cues as in vitro models for investigating cell‐mediated mechanisms driving tissue healing and regeneration.