bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-particle cryo-EM structure of the outer hair cell motor protein prestin.
Authors: Navaratnam Dhasakumar , Butan Carmen , Song Qiang , Bai Jun-Ping , Tan Winston , Santos-Sacchi Joseph 
Published: September 2021

Abstract
The mammalian outer hair cell (OHC) protein prestin (Slc26a5), a member of the solute carrier 26 (Slc26) family of membrane proteins, differs from other members of the family owing to its unique piezoelectric-like property that drives OHC electromotility. OHCs require prestin for cochlear amplification, a process that enhances mammalian hearing. Despite substantial biophysical characterization, the mechanistic basis for the prestin’s electro-mechanical behavior is not fully understood. To gain insight into such behavior, we have used cryo-electron microscopy at subnanometer resolution (overall resolution of 3.96Å) to investigate the three-dimensional structure of prestin from gerbil (Meriones unguiculatus). Our studies show that prestin dimerizes with a 3D architecture strikingly similar to the dimeric conformation observed in the Slc26a9 anion transporter in an inside open/intermediate state, which we infer, based on patch-clamp recordings, to reflect the contracted state of prestin. The structure shows two well-separated transmembrane (TM) subunits and two cytoplasmic sulfate transporter and anti-sigma factor antagonist (STAS) domains forming a swapped dimer. The dimerization interface is defined by interactions between the domain-swapped STAS dimer and the transmembrane domains of the opposing half unit, further strengthened by an antiparallel beta-strand at its N terminus. The structure also shows that each one of its two transmembrane subunits consists of 14 transmembrane segments organized in two inverted 7-segment repeats with a topology that was first observed in the structure of bacterial symporter UraA (Lu F, et al., Nature 472, 2011). Finally, the solved anion binding site structural features of prestin are quite similar to that of SLC26a9 and other family members. Despite this similarity, we find that SLC26a9 lacks the characteristic displacement currents (or nonlinear capacitance (NLC)) found with prestin, and we show that mutation of prestin’s Cl- binding site removes salicylate competition with anions in the face of normal NLC, thus refuting the yet accepted extrinsic voltage sensor hypothesis and any associated transport-like requirements for voltage-driven electromotility.
Comprehensive In Vivo and In Silico Approaches to Explore the Hepatoprotective Activity of Poncirin Against the Paracetamol Toxicity
Authors: Ullah Hadayat , Khan Ashrafullah , Alameen Alaa Alnoor , Alaqil Faten Abdullah , Ali Yousif Salah , Ahmad Sajjad , AlSharari Shakir D. , Khan Salman 
Published: September 2021

Abstract
Purpose: In the present study, the Poncirin was evaluated against the Paracetamol-induced liver injury using in vivo and computational approaches. Methods: The Paracetamol was administered intraperitoneally to establish the liver injury in mice and subsequently, to investigate the hepatoprotective effect of the Poncirin on the liver injury. The effect of the Poncirin was evaluated against the liver injury markers and inflammatory cytokines. Similarly, in the present study the antioxidants and oxidative stress parameters were also assessed following paracetamol-induced liver injury. The histological studies following liver injury was also assessed using H and E staining, Masson’s trichrome staining, and periodic acid Schiff staining. Results: The Poncirin markedly improved the antioxidant enzymes, while attenuated the oxidative stress markers and inflammatory cytokines. The Poncirin also markedly improved hematological parameters and electrolytes profile. Furthermore, the Poncirin treatment significantly improved the histological parameters using H and E staining, Masson’s trichrome and PAS staining compared to the control. The Poncirin treatment also improved the liver function tests and liver synthetic activity compared to Paracetamol treated group. The immunohistochemistry analysis revealed significant decrease in the inflammatory signaling protein such as NF-κB (nuclear factor kappa light chain enhancer of activated B cells), JNK (Jun N-terminal Kinase) and COX-2 (Cyclooxygenase-2) expression level compared to the Paracetamol treated group. The in silico approach was also used to analyze the potential activity and explore the underlying molecular mechanism of Poncirin. Conclusion: The Poncirin improved the sign and symptoms associated with the liver injury using both in vivo and computational approaches.
Emergence of Two Distinct Variants of SARS-CoV-2 and Explosive Second Wave of COVID-19: An Experience From A Tertiary Care Hospital, Pune, India
Authors: Shrivastava Shubham , Mhaske Suhas T , Modak Meera S , Virkar Rashmi G , Pisal Shamburaje S , Mishra Akhilesh Chandra , Arankalle Vidya A 
Published: September 2021

Abstract
The emergence of novel variants of SARS-CoV-2 in several countries has been associated with the increased transmission/ reduced neutralization potential of antibodies against the Wuhan virus (wild type). Currently, India is recovering from an explosive second wave of COVID-19. This prospective study was conducted quarterly for one year (May 2020 to June 2021) at a tertiary care hospital, Pune city, western India. Receptor binding domain (RBD, n = 319) and full genome (n = 20) sequences from viral RNA positive nasopharyngeal swabs of COVID-19 patients representing first and second waves were used for analysis. We did not detect Brazil, South Africa and California variants. Till December, only wild type strain was prevalent. Concurrent with the upsurge of second wave in March-2021, 73% (33/45) of RBD sequences harboured L452R/E484Q mutations characteristic of Kappa variant. In April, co-circulation of Kappa (37%) and Delta (L452R/T478K, 59%) variants was recorded. During May and June, delta variant became the predominant circulating variant and coincided with a significant decline in the number of COVID-19 cases. Of the 20 full genome sequences, six isolates each exhibited signature mutations of Kappa and Delta variants respectively. With several states witnessing reduction in the number of COVID-19 cases, continuous monitoring of newer mutations and assessment of these mutations in influencing virus transmissibility and impact on vaccinated / previously exposed individuals would be necessary.
Effect of Femoral Nerve Block with Different Concentrations of Chloroprocaine on the Recovery of Joint Function in Rehabilitation Training after Knee Replacement: A Prospective, Double-Blind, Randomized, Controlled Clinical Study
Authors: Li Jiajia , Xia Ruiqiang , Zhu Chunchun , Wu Hong , Liu Haoran , Wang Zhanghong , Wang Haixing , Li Jun , Ma Jianfeng 
Published: September 2021

Abstract
Background: Patients who undergo total knee arthroplasty (TKA) experience severe pain after surgery. Especially active pain in early postoperative rehabilitation training of the knee joint is particularly severe, and it should receive people’s attention.Methods: A total of 90 patients who only received unilateral TKA in our hospital were randomly and equally divided into three groups (group C1: 1% chloroprocaine, group C2: 2% chloroprocaine, and group NS: 0.9% sodium chloride solution 0.2 ml/kg; the dosage was fixed at 0.2 ml/kg for all three groups). All patients received femoral nerve catheterization before TKA and started rehabilitation training 48 h after TKA. The visual analogue scale (VAS) scores of active exercises before and after administration were observed and recorded. VAS scores, maximum knee flexion and extension angles, the incidence of knee flexion angle ≥100° in each group, the American knee society(AKS) scores, together with postoperative rehabilitation training satisfaction and adverse effects were recorded at 7 days and 3 months after surgery.Results: Compared with the NS group, VAS scores after administration of patients in the group C1 and C2 were decreased significantly at each time point (P < 0.05), and the maximum knee flexion angles were increased significantly (P < 0.05), as well as the proportion of maximum knee angle ≥100° (P < 0.05). The postoperative rehabilitation training satisfaction of patients in group C1 and C2 were more than that of patients in the NS group (P < 0.05).Conclusion: The administration of 1% chloroprocaine for femoral nerve block before rehabilitation training after TKA could improve the knee flexion angle at the early postoperative stage, increase the proportion of patients who could squat, and cause fewer side effects.
An Insight Into The MicroRNA Profiles of An Ectoparasite Mite Varroa Destructor (Acari: Varroidae), The Primary Vector of Deformed Wing Virus (DWV) of The Honey Bee
Authors: Kumar Deepak , Alburaki Mohamed , Tahir Faizan , Goblirsch Michael , Adamczyk John , Karim Shahid 
Published: September 2021

Abstract
The most important ectoparasite of the honeybee is the remarkably adaptive mite Varroa destructor. The Varroa mite is a competent vector of Deformed Wing Virus (DWV), the Varroa-virus complex is one of the main factors associated with elevated annual honey bee colony mortality. Micro-RNAs (miRNAs) are small, non-coding RNAs of ~22-24 nucleotides, produced by all plants, animals, and viruses that influence biological processes through post-transcriptional regulation of gene expression. Knowledge of miRNAs and their functional role in mite biology remains limited. This study developed small RNA libraries from male and female V. destructor by utilizing Illumina's small RNA-Seq platform. A total of 101,913,208 and 91,904,732 small RNA reads (>18 nucleotides) from male and female mites were analyzed using the mirDeep2 algorithm. A conservative approach predicted a total of 306 miRNAs, of which 18 were upregulated and 13 were downregulated in female V. destructor compared to males. A qPCR assay validated the expression of selected differentially expressed female Varroa miRNAs. This dataset provides a list of potential miRNA targets involved in regulating vital Varroa biological processes and for deciphering new targets against Varroa and honey bee viruses they carry.
Differentiation of Multipotent Stem Cells to Insulin-Producing Cells for Treatment of Diabetes Mellitus: Bone Marrow- and Adipose Tissue-Derived Cells Comparison
Authors: Eydian Zahra , Ghasemi Alaleh Mohammad , Ansari Samira , Kamali Ali Naghi , Khosravi Maryam , Momtaz Sima , Riki Sanaz , Rafighdoost Laleh , Heravi Reza Entezari 
Published: September 2021

Abstract
Background: Mesenchymal stem cells (MSCs) from human adipose tissue and bone marrow have a great potential for use in cell therapy due to their ease of isolation, expansion, and differentiation. Our intention was to isolate and promote in vitro expansion and differentiation of MSCs from human adipose and bone marrow tissue into cells with a pancreatic endocrine phenotype and to compare the potency of these cells together.Methods and Results: MSCs were pre-induced with nicotinamide, mercaptoethanol, B-27 and b-FGF in L-DMEM for 2 days and re-induced again in supplemented H-DMEM for another 3 days. Expression of five genes in differentiated beta cells was evaluated by Real-time PCR and western blotting and the potency of insulin release in response to glucose stimulation was evaluated by insulin and C-peptide ELISA kit.Quantitative RT-PCR results showed up-regulation of four genes in differentiated beta-islet cells (Insulin, Ngn-3, Pax-4 and Pdx-1) compared with the control. Western blot analysis showed that MSCs cells mainly produced proinsulin and insulin after differentiation but nestin was more expressed in pre-differentiated stem cells. Glucose and insulin secretion assay showed that insulin levels and C-peptide secretion were significantly increased in response to 10 mM glucose.Conclusions: Our study showed that both adipose and bone marrow stem cells could differentiate into functional beta-islet cells but it seems that adipose stem cells could be a better choice for treatment of diabetes mellitus according to their more safety and potency.
Development of a multifunctional nanocomposite film with record-high ultralow temperature toughness and unprecedented fatigue-resistance
Authors: Jiang Shuaicheng , Wei Yanqiang , Li Jiongjiong , Li Xiaona , Wang Kaili , Li Kuang , Shi Sheldon , Li Jianzhang , Fang Zhen 
Published: September 2021

Abstract
In the quest of materials that can tolerate extreme environments (i.e., aerospace, polar regions of earth), facile design of self-healing, high fatigue-resistant and multifunctional nanocomposite materials with excellent ultralow temperature toughness, especially by utilizing inexpensive and sustainable bioresources is still currently challengeable. In current study, we present a material that displays remarkable ultralow temperature toughness, shows excellent toughness (107.3 MJ·m-3) at − 196°C and maintains high mechanical strength in highly humid environments. This material is a spider silk-inspired, poly(vinyl alcohol) (PVA)-based, autonomous room temperature self-healable nanocomposite by complexation of boron nitride (BN), quantum dots (QDs) and soybean protein isolate grafted lignin (SPI-lignin). The fabricated material, namely PVA-BN-QDs-SPI-lignin, simultaneously exhibits outstanding tensile strength (53.3 MPa), toughness (182.8 MJ·m-3), fatigue-resistance as well as antiultraviolet and fluorescent properties and sets an impressive new record of folding-failure (900 000 times) and toughness, which are 10.6 to 45.7 times higher than other graphene-based nanocomposites. It can be impressively self-healed within only 2 minutes. Of particular interest is its facile, green, mild and inexpensive preparation method that can be easily scale up. It is believed that this work, beginning with abundant biodegradable resources, opens the door to develop biobased multifunctional materials in practical applications, such as flexible wearable materials.
A Patient With Turner Syndrome Recieved the Percutaneous Vertebroplasty Seven Times: a Case Report and Literature Review
Authors: Li Longyu , Shi Yifang , Zhao Nan , Liu Zhengpei , Zhao Zhe , Song Zongmian , Zheng Sailei , Yan Miaoheng , Leng Zikuan , Chen Songfeng , Shang Guowei , Kou Hongwei , Liu Hongjian 
Published: September 2021

Abstract
Background Turner syndrome (TS) is characterized as the complete or partial absence of one X chromosome and is an extremely rare disease affecting approximately 1:2,500 live female births. Though the prevalence of osteoporosis among women with TS is estimated to be around 55-64% and they suffer more frequently from fractures than normal, few reports concerning TS patients with osteoporosis are able to be seen due to tiny number of patients. Case presentation Here we report a rare case of TS with osteoporosis, who has undergone percutaneous vertebroplasty (PVP) seven times because of several vertebral compression fractures (VCFs). G-banded karyotype analysis was performed and the result was 45,X[43]/47,XXX[17], indicating that the patient was a mosaicism of TS karyotype and Trisomy X syndrome karyotype. TS is the underlying cause of low level of estrogen for this patient. The interaction of aging, estrogen deficiency and intestinal dysbacteriosis leads to her severe osteoporosis and multi-segmental VCFs. The aim of this report is to provide recommendations regarding the management of TS patients with osteoporosis by reviewing the clinical presentation of TS, the influence of estrogen deficiency in osteoporosis, etc.Conclusions Early diagnosis and hormone replacement treatment are essential to prevent osteoporosis and reduce the risk of fractures. This is a rare case report describing TS patient with severe osteoporosis and VCFs.
Emergence of Climate Change in the Tropical Pacific
Authors: Ying Jun , Collins Matthew , Cai Wenju , Timmermann Axel , Huang Ping , Chen Dake , Stein Karl 
Published: September 2021

Abstract
Future changes in both the mean climate of the tropical Pacific and characteristics of the El Niño–Southern Oscillation (ENSO) are now established as being likely. Determining the time of emergence (ToE) of detectable climate change signals against background noise of natural variability is critical to mitigation strategies and adaptation planning. Here, we find that the annual-mean SST signal, mainly reflecting the tropical-mean warming signal, has already emerged in the historical period across much of the tropical Pacific, with the latest ToE in the east. The annual-mean rainfall signal is expected to emerge by around mid-century based on the multi-model ensemble mean (MEM) result, with some sensitivity to emission scenarios. By contrast, the signal of ENSO-related rainfall variability is projected to emerge by around 2040 ± 3 based on the MEM regardless of emission scenarios, ~ 30 years sooner than that of the ENSO-related SST variability. Our results are instructive for detection of climate change signals in the tropical Pacific and reinforce the severe risks of ENSO-induced climate extremes that are fast emerging regardless of any mitigation actions.
A rare case of early massive monomuscular fibrosis causing severe unilateral euthyroid Graves’ ophthalmopathy in a smoker patient with dyslipidemia
Authors: Frazzetto Giuseppe , Arpi Maria Luisa , Regalbuto Concetto , Belfiore Antonino , Frasca Francersco , Moli Rosario Le 
Published: September 2021

Abstract
BackgroundGraves’ ophtahlmopathy (GO) is an autoimmune manifestation of orbit affecting about 25% of patients with Graves’ disease (GD). Autoreactive T cells involved in thyroid autoimmunity can recognize the thyroid stimulating receptor (TSHr) expressed in orbit tissues of GO patients. Clinical manifestations of GO are rather different depending of the presence of some risks factors as smoke, hyperthyroidism duration, age, biological activity of anti TSHr antibodies (TSH-R-Ab) and metabolic diseases.Case presentation:here we present a rare case of euthyroid single muscular GO in a 50 years old patient, he was smoker and had dyslipidemia from several years. The patient experienced a very rapid and severe depression of ocular motility of the right eye that causes an uncorrectable and constant diplopia severely affecting his quality of life. He was euthyroid and TSH-R-Ab plasmatic levels were only slightly elevated. Intravenous corticosteroids pulse therapy was partially effective and two rounds of wall orbital surgical decompression was necessary. A massive mono-muscular fibrosis was evidenced by biopsy of right inferior rectus muscle.Conclusionssevere unilateral, mono-muscular GO in a euthyroid Graves’ patient was found to be sustained by rapid and massive fibrosis of the inferior rectus muscle of right orbit, the clarification of pathogenetic mechanisms of these GO clinical forms requires further studies.
Large-gap Peripheral Nerve Repair Using Xenogeneic Transplants in Primates
Authors: Holzer Paul , Chang Elizabeth , Tarlton Jamie , Lu Diana , Gillespie Natasha , Rogers Kaitlyn , Adkins Jon , Metea Monica , LaRochelle Alan , Wicks Joan , Onel Buket , Gullans Steve , Doloff Joshua , Scobie Linda , Cetrulo Curt , Monroy Rod 
Published: September 2021

Abstract
Early surgical intervention is required to successfully treat severe, large-gap peripheral nerve injuries. However, all existing treatments have shortcomings, and for large-gap injuries (≥4 cm), there is no reported alternative to autologous nerve. We report preclinical repair of large (4 cm), complete transectional radial nerve damage in Rhesus macaques using viable, whole sciatic nerve from genetically engineered, designated pathogen free porcine donors. Porcine nerves are physiologically similar to human nerves, contain neurotrophic growth factors and a matrix-rich scaffold, and offer greater clinical availability. We demonstrate regeneration of the transected nerve, distal muscle reinnervation, and recovery of conduction velocity and compound muscle action potential across xenogeneic transplants resulting in functional recovery comparable to autologous controls. We also show the lack of systemic porcine cell migration and the elimination of detectable transplanted porcine tissue. Our findings support the safety and efficacy of neural porcine therapeutics and the broader clinical potential of xenotransplantation.
Correlates of Neutralizing/SARS-CoV-2-S1-binding Antibody Response with Adverse Effects and Immune Kinetics in BNT162b2-Vaccinated Individuals
Authors: Maeda Kenji , Amano Masayuki , Uemura Yukari , Tsuchiya Kiyoto , Matsushima Tomoko , Noda Kenta , Shimizu Yosuke , Fujiwara Asuka , Takamatsu Yuki , Ichikawa Yasuko , Nishimura Hidehiro , Kinoshita Mari , Matsumoto Shota , Gatanaga Hiroyuki , Yoshimura Kazuhisa , Oka Shinichi , Mikami Ayako , Sugiura Wataru , Sato Toshiyuki , Yoshida Tomokazu , Shimada Shinya , Mitsuya Hiroaki 
Published: September 2021

Abstract
While mRNA vaccines against SARS-CoV-2 are exceedingly effective in preventing symptomatic infection, their immune response features remain to be clarified. In the present prospective study, 225 healthy individuals in Japan, who received two BNT162b2 doses, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT50; assessed using infectious virions) with various determinants were examined and the potency of serums against variants of concerns was determined. Significant rise in NT50s was seen in serums on day 28 post-1st dose. A moderate inverse correlation was seen between NT50s and ages, but no correlation seen between NT50s and adverse effects. NT50s and SARS-CoV-2-S1-binding-IgG levels on day 28 post-1st dose and pain scores following the 2nd shot were greater in women than in men. The average half-life of NT50s was ~ 68 days and the estimated average time length till the total disappearance of neutralizing activity was ~ 198 days. While serums from elite-responders (NT50s > 1,500-fold: the top 4% among the participants) potently to moderately blocked all variants of concerns examined, some serums with low NT50s failed to block the B.1.351-beta strain. Since BNT162b2-elicited immunity against SARS-CoV-2 is short, an additional vaccine or other protective measures are needed.