Miracle-dz/UniFAR-FTUs huggingface dataset:
Nephroprotection by SGLT2i in CKD Patients: May It Be Modulated by Low-Protein Plant-Based Diets?

Sodium-glucose-transporter 2 inhibitors (SGLT2i) are a new class of anti-diabetic drugs that in large trials such as CREDENCE have shown also a reduction of glomerular hyperfiltration and albuminuria in type 2 diabetic patients. Hence, the interest toward SGLT2i is focused toward this potential nephroprotective effect, in order to reduce the progression to overt nephropathy, and it seems to be confirmed in the most recent DAPA-CKD trial. This is the reason why the indication for SGLT2i treatment has been extended to chronic kidney disease (CKD) patients with eGFR up to 30 ml/min, namely with CKD stage 1–3. In patients with CKD stage 3 to 5, the most recent KDIGO guidelines recommend low-protein diet and plant-based regimens to delay end-stage kidney disease (ESKD) and improve quality of life. Similarly to SGLT2i, low-protein diets exert renal-protective effects by reducing single nephron hyperfiltration and urinary protein excretion. Beyond the glomerular hemodynamic effects, both protein restriction and SGLT2i are able to restore autophagy and, through these mechanisms, they may exert protective effects on diabetic kidney disease. In this perspective, it is likely that diet may modulate the effect of SGLT2i in CKD patients. Unfortunately, no data are available on the outcomes of the association of SGLT2i and low-protein and/or vegan diets. It is therefore reasonable to investigate whether CKD patients receiving SGLT2i may have further advantages in terms of nephroprotection from the implementation of a low-protein and/or plant-based diet or whether this association does not result in an additive effect, especially in vascular nephropathies.
Correlational Analysis of ALS Progression and Serum NfL Measured by Simoa Assay in Chinese Patients

Background: Neurofilament light chain (NFL) was believed to be a promising biomarker for the diagnosis of Amyotrophic lateral sclerosis (ALS) and disease burden evaluation. Objective: To determine the serum NFL level and its clinical relevance, including its association with disease severity [evaluated by the ALS Functional Rating Scale–revised (ALSFRS-r) score and King's College staging system] and progression (evaluated by the disease progression rate (DPR) and diagnostic delay), in ALS patients in China. Method: Serum NFL levels were detected using the Single Molecule Array (Simoa) technology in 30 ALS patients and 20 healthy controls (HCs). Results: There were significantly elevated levels of serum NFL in patients with ALS than in the HCs (P < 0.001). The serum NFL levels were significantly higher in rapidly progressive ALS and patients in Stage 3 than in slowly progressive ALS and patients in Stage 2 (PDPR < 0.001, PDiagnosticdelay = 0.019; Pstage= 0.033). Furthermore, the serum NFL levels negatively correlated with the diagnostic delay (R2 = 0.23, P = 0.016), the ALSFRS-r score (R2 = 0.15, P = 0.047) and disease duration (R2 = 0.15, P = 0.034), and positively correlated with the DPR (R2 = 0.42, P < 0.001). Conclusions: The present study preliminarily investigated the diagnostic value of serum NFL and its clinical relevance in the Chinese ALS population using the ultrasensitive Simoa technology. The results demonstrated that the level of serum NFL may become a potential biomarker for ALS diagnosis and indicate disease severity and progression.
MicroRNA-221/222 Mediates ADSC-Exosome-Induced Cardioprotection Against Ischemia/Reperfusion by Targeting PUMA and ETS-1

Cardiovascular disease is a major health problem in industrialized and developing countries and is the leading cause of death and disability. Myocardial ischemia/reperfusion (I/R) causes cardiomyocyte damage such as apoptosis and hypertrophy. The purpose of this study was to investigate the effects of exosomes from adipose-derived stem cells (ADSC-Exo) on hearts from I/R mice and to explore the underlying mechanisms. ADSC-Exo significantly decreased I/R-induced cardiomyocyte apoptosis and hypertrophy, as detected by TdT-mediated dUTP nick end-labeling (TUNEL) and wheat germ agglutinin (WGA) staining, respectively. In addition, the expression of apoptosis-related proteins p-p53 and PUMA and hypertrophy-related proteins ETS-1 and ANP were significantly reduced in the cardiomyocytes of ADSC-Exo-treated I/R mice compared to those of control mice. Both PUMA and ETS-1 are reported to be target genes for miR-221/222. I/R operation significantly reduced miR-221/222 expression, while ADSC-Exo treatment increased miR-221/222 expression, as detected by RT-qPCR. We also observed that cardiac I/R operation markedly increased cell apoptosis and hypertrophy in miR-221/222 knockout (KO) mice, while ADSC-Exo reduced the effects of I/R operation. Furthermore, ADSC-Exo protected H9c2 cardiomyocytes from H2O2-induced damage by reducing apoptosis and hypertrophy in vitro. H2O2 treatment significantly reduced miR-221/222 expression, while ADSC-Exo treatment reversed this effect in H9c2 cells. ADSC-Exo treatment decreased H2O2-induced PUMA and ETS-1 expression. Compared with control treatment, I/R treatment significantly reduced p-AKT and increased p-p65, while ADSC-Exo and miR-221/222 mimics attenuated these effects. The AKT activator SC79 and p65 inhibitor Bay 11-7082 reduced H2O2-induced cell apoptosis and hypertrophy. Based on these findings, ADSC-Exo prevents cardiac I/R injury through the miR-221/miR-222/PUMA/ETS-1 pathway. Therefore, ADSC-Exo is an effective inhibitor of I/R-induced heart injury.
Redefining Criteria to Ensure Adequate Sentinel Lymph Node Biopsy With Dual Tracer for Breast Cancer

Background For sentinel lymph node biopsy (SLNB) in patients with breast cancer, the dual tracer of blue dye and radioisotope with the 10% rule that all nodes with radioactive count of 10% or more of the hottest node ex vivo should be removed is widely accepted. However, the cut-off point of radioactivity is being questioned for possibly excessive removal of negative nodes. Methods To compare different percentile rules and optimize the criteria for identifying SLNs, we established a database which prospectively collected the radioactivity, status of blue dye and the pathological results of each SLN in breast cancer patients who successfully underwent SLNB with a combination of methylene blue and radioisotope. Results A total of 2,529 SLNs from 1,039 patients were identified from August 2010 to August 2019. 16.4% (414/2,529) positive nodes were removed at a cost of 83.6% (2115/2,529) negative nodes removed excessively. Up to 17.9% (375/2,115) negative nodes were removed as radioactively hot nodes without blue staining. By gradually increasing the threshold by each 10%, the number of negative nodes identified reduced by 18.2% (385/2,115) with only three node-positive patients (1.0%) missed to be identified using the “40% + blue” rule. In patients with ≥ 2 SLNs removed, 12.3% (238/1,942) negative nodes avoided unnecessary removal with only 0.8% (2/239) positive patients missed with the “hottest two + blue” rule. Conclusions Our data indicated that the “40% + blue” rule or the “hottest two + blue” rule for SLNB with the dual tracer of blue dye and radioisotope may be considered as a potential alternative rule to minimize extra nodes resected. Nonetheless, it should be validated by prospective trials with long-term follow-up.
Influence of Knowledge Management Practices on Entrepreneurial and Organizational Performance: A Mediated-Moderation Model

This study aims to identify the influence of knowledge management practices on the entrepreneurial and organizational performance with the mediating effect of dynamic capabilities and moderating role of opportunity recognition. Data were gathered from 486 entrepreneurs and applied a structural equation model to test the hypotheses. We found that knowledge management practices have a positive and significant influence on dynamic capabilities, as well as have a significant impact on entrepreneurial and organizational performance. Moreover, results indicated that dynamic capabilities partially mediate in the relationship between knowledge management practices on entrepreneurial and organizational performance. Furthermore, the relationship between knowledge management practices with entrepreneurial and organizational performance strengthening by opportunity recognition. Further, implications and limitations were discussed in the paper.
Architectural design and phase engineering of N/B-codoped TiO2(B)/anatase nanotube assemblies for high-rate and long-life lithium storage

TiO2 polymorphs hold great promise as anode candidates in lithium-ion batteries (LIBs) because of their low cost, enhanced safety and high power capability, but they suffer from poor electrical conductivity and low lithium-ion mobility. Herein, an attractive nanoassembly made of ultrathin TiO2 nanotubes with selected phases and hetero-atom doping was developed through a mild ionothermal reaction. The grain interface of TiO2(B)/anatase, N/B codoping, and nanoassembly were elaborately engineered. They offer effective nanohighways for fast electronic and Li-ion transport, when applied as an anode in LIBs. The carbon-free, N/B-codoped TiO2(B)/anatase nanotube nanoassemblies exhibit exceptionally high rate capability and good durability (160 mA h g−1 at 12 A g−1 and retaining 140 mA h g−1 even after 500 cycles). This work demonstrates that the integrated design of surface states and electronic structures plays a crucial role in exploring new capabilities of TiO2 polymorphs for electrochemical energy storage.
Protective Effects of p53 Regulatory Agents Against High-LET Radiation-Induced Injury in Mice

Radiation damage to normal tissues is one of the most serious concerns in radiation therapy, and the tolerance dose of the normal tissues limits the therapeutic dose to the patients. p53 is well known as a transcription factor closely associated with radiation-induced cell death. We recently demonstrated the protective effects of several p53 regulatory agents against low-LET X- or γ-ray-induced damage. Although it was reported that high-LET heavy ion radiation (>85 keV/μm) could cause p53-independent cell death in some cancer cell lines, whether there is any radioprotective effect of the p53 regulatory agents against the high-LET radiation injury in vivo is still unclear. In the present study, we verified the efficacy of these agents on bone marrow and intestinal damages induced by high-LET heavy-ion irradiation in mice. We used a carbon-beam (14 keV/μm) that was shown to induce a p53-dependent effect and an iron-beam (189 keV/μm) that was shown to induce a p53-independent effect in a previous study. Vanadate significantly improved 60-day survival rate in mice treated with total-body carbon-ion (p < 0.0001) or iron-ion (p < 0.05) irradiation, indicating its effective protection of the hematopoietic system from radiation injury after high-LET irradiation over 85 keV/μm. 5CHQ also significantly increased the survival rate after abdominal carbon-ion (p < 0.02), but not iron-ion irradiation, suggesting the moderate relief of the intestinal damage. These results demonstrated the effectiveness of p53 regulators on acute radiation syndrome induced by high-LET radiation.
CACNA1A Gene Variants in Eight Chinese Patients With a Wide Range of Phenotypes

Background: The CACNA1A gene encodes the voltage-dependent P/Q-type calcium channel subunit alpha-1A, which is widely expressed throughout the CNS. The biological roles of the P/Q channel are diverse and the phenotypic spectrum caused by CACNA1A mutations is wide. The aim of this study is to demonstrate its phenotypic diversity and analyze the genotype-phenotype correlations in a cohort of Chinese patients. Methods: Patients with hemiplegic migraine, cerebellar ataxia, developmental delay, or epilepsy without known causes were tested by trios whole-exome sequencing. Patients with pathogenic CACNA1A gene variants were recruited. The clinical information of the patients was collected, and the association between the genotype and the phenotype was investigated. Results: In total, eight patients (six females and two males) were found to have CACNA1A gene variants. All the variants were de novo including six missense variants and one frameshift variant. Four de novo missense variants were found in five patients located in the S4, S5, or S6 transmembrane segments of Domain II and III (p.R1352Q, p.G701V, p.A713T, p.V1393M). All of them were correlated with severe phenotypes, including three with sporadic hemiplegic migraine type 1 and epilepsy, and two with developmental and epileptic encephalopathy. The other two missense variants, p.Y62C and p.F1814L, located in the cytoplasmic side of the N-terminus and C-terminus, respectively. The variant p.Y62C was associated with severe hemiconvulsion-hemiplegia-epilepsy syndrome, and p.F1814L was associated with relatively mild phenotypes. All the missense variants were speculated as gain-of-function (GOF) mutations. The only frameshift variant, p.Q681Rfs*100, a lose-of-function (LOF) mutation, was found in a patient with episodic ataxia type 2. Meanwhile, all the patients had developmental delay ranging from mild to severe, as well as cerebellar ataxia including one with congenital ataxia, one with episodic ataxia, and six with non-progressive ataxia. Conclusions: CACNA1A variants could lead to a wide spectrum of neurological disorders including epileptic or non-epileptic paroxysmal events, cerebellar ataxia, and developmental delay. The variants could be both GOF and LOF mutations. There appeared to be some correlations between genotypes and phenotypes.
Technical Determinants of On-Water Rowing Performance

Purpose: Research establishing relationships between measures of rowing technique and velocity is limited. In this study, measures of technique and their effect on rowing velocity were investigated. Methods: Ten male singles, eight female singles, three male pairs, and six female pairs participated. Data from each stroke for forty-seven 2,000 m races were collected using Peach PowerLine and OptimEye S5 GPS units. General linear mixed modeling established modifying effects on velocity of two within-crew SD of predictor variables for each boat class, with subsequent adjustment for power, and for power and stroke rate in separate analyses. Twenty-two predictor variables were analyzed, including measures of boat velocity, gate force, and gate angle. Results were interpreted using superiority and inferiority testing with a smallest important change in velocity of 0.3%. Results: Substantial relationships with velocity were found between most variables assessed before adjustment for power, and for power and stroke rate. Effect magnitudes were reduced for most variables after adjustment for power and further reduced after adjustment for stroke rate and power, with precision becoming inadequate in many effects. The greatest modifying effects were found for stroke rate, mean and peak force, and power output before adjustment, and for catch angle after adjustment for stroke rate and power. Substantial between-crew differences in effects were evident for most predictors in some boat classes before adjustment and in some predictors and some boat classes after adjustment for stroke rate and power. Conclusion: The results presented reveal variables associated with improvements in rowing performance and can be used to guide technical analysis and feedback by practitioners. Higher stroke rates and greater catch angles should be targeted to improve rowing performance, and rower force development for the improvement of power output. Relationships between rowing technique and velocity can be crew-dependent and are best assessed on an individual basis for some variables.
A Novel Nanosystem Realizing Curcumin Delivery Based on Fe3O4@Carbon Dots Nanocomposite for Alzheimer’s Disease Therapy

Alzheimer’s disease (AD) is the most common neurodegenerative disease, which seriously affects human health but lacks effective treatment methods. Amyloid β (Aβ) aggregates are considered a possible target for AD treatment. Evidence is increasingly showing that curcumin (CUR) can partly protect cells from Aβ-mediated neurotoxicity by inhibiting Aβ aggregation. However, the efficiency of targeted cellular uptake and bioavailability of CUR is very low due to its poor stability and water-solubility. In order to better improve the cell uptake efficiency and bioavailability of CUR and reduce the cytotoxicity of high-dose CUR, a novel CUR delivery system for AD therapy has been constructed based on the employment of the Fe3O4@carbon dots nanocomposite (Fe3O4@CDs) as the carrier. CUR-Fe3O4@CDs have a strong affinity toward Aβ and effectively inhibit extracellular Aβ fibrillation. In addition, CUR-Fe3O4@CDs can inhibit the production of reactive oxygen species (ROS) mediated by Aβ fibrils and the corresponding neurotoxicity in PC12 cells. More importantly, it can restore nerve damage and maintained neuronal morphology. These results indicate that the application of CUR-Fe3O4@CDs provides a promising platform for the treatment of AD.
Case Report: Distinctive EEG Patterns in SCARB-2 Related Progressive Myoclonus Epilepsy

Action myoclonus-renal failure syndrome (AMRF) is a rare, recessively inherited form of progressive myoclonus epilepsy (PME) caused by mutations in the SCARB2 gene and associated with end-stage renal failure. In addition to severe progressive myoclonus, the neurological manifestations of this syndrome are characterized by progressive ataxia and dysarthria with preserved intellectual capacity. Since its original description, an increasing number of “AMRF-like” cases without renal failure have been reported. We describe the case of a 29-year-old woman with progressive disabling myoclonus associated with dysarthria and ataxia who was found to have a novel homozygous frameshift mutation in the SCARB2 gene. In addition, this report emphasizes the presence of two EEG patterns, fixation-off phenomenon, and bursts of parasagittal spikes exclusively seen during REM sleep that appear to be characteristic of this condition.
Caught in the Crossfire: How Contradictory Information and Norms on Social Media Influence Young Women’s Intentions to Receive HPV Vaccination in the United States and China

This study uses online survey data from the United States and China to examine how contradictory information and social norms regarding HPV vaccines obtained through social media are related to young women’s attitudes and intentions surrounding HPV vaccination. The results show that exposure to contradictory information on social media had a greater negative association with intentions to receive HPV vaccination among the United States participants than among the Chinese participants, while social norms supporting HPV vaccines had a stronger positive association with intentions to receive HPV vaccination among the Chinese participants than among the United States participants. These findings extend the literature on social media communication regarding HPV vaccination and contribute to our knowledge of cultural contexts that influence intentions to receive HPV vaccination.
Infection of Ophiocordyceps sinensis Fungus Causes Dramatic Changes in the Microbiota of Its Thitarodes Host

The Chinese cordyceps is a unique and valuable parasitic complex of Thitarodes/Hepialus ghost moths and the Ophiocordyceps sinensis fungus for medicine and health foods from the Tibetan Plateau. During artificial cultivation of Chinese cordyceps, the induction of blastospores into hyphae is a prerequisite for mummification of the infected Thitarodes larvae. To explore the microbial involvement in the induction of mycelia-blastospore transition, the microbiota of the hemolymph and gut from Thitarodes xiaojinensis larvae with or without injected O. sinensis blastospores were investigated by culture-dependent and -independent methods. Twenty-five culturable bacterial species and 14 fungal species, together with 537 bacterial operational taxonomic units (OTUs) and 218 fungal OTUs, were identified from the hemolymph and gut of samples from five stages including living larvae without injected fungi (A) or with high blastospore load (B), mummifying larvae without mycelia coating (C), freshly mummifying larvae coated with mycelia (D), and completely mummified larvae with mycelia (E). Two culturable bacterial species (Serratia plymuthica, Serratia proteamaculans), and 47 bacterial and 15 fungal OTUs were considered as shared species. The uninfected larval hemolymph contained 13 culturable bacterial species but no fungal species, together with 164 bacterial and 73 fungal OTUs. To our knowledge, this is the first study to detect large bacterial communities from the hemolymph of healthy insect larvae. When the living larvae contained high blastospore load, the culturable bacterial community was sharply inhibited in the hemolymph but the bacterial and fungal community greatly increased in the gut. In general, high blastospore load increased bacterial diversity but sharply decreased fungal diversity in the hemolymph and gut by OTUs. The bacterial loads of four culturable species (Chryseobacterium sp., Pseudomonas fragi, S. plymuthica, S. proteamaculans) increased significantly and O. sinensis and Pseudomonas spp. became dominant microbes, when the infected larvae became mummified, indicating their possible involvement in the larval mummification process. The discovery of many opportunistic pathogenic bacteria in the hemolymph of the healthy larvae, the larval microbial diversity influenced by O. sinensis challenge and the involvement of dominant bacteria during larval mummification process provide new insight into the infection and mummification mechanisms of O. sinensis in its Thitarodes hosts.
Influence of Aerobic Exercise After Static Stretching on Flexibility and Strength in Plantar Flexor Muscles

Aerobic exercise could improve stretch-induced strength deficits. However, mechanisms of the improvement were unclear. The purpose of the study was to examine the effects of aerobic exercise after static stretching (SS) on flexibility and isometric strength in ankle plantar-flexor muscles. Fifteen healthy males received two interventions after SS of their ankle plantar-flexor muscles for 5 min. One was aerobic exercise for 10-min on a cycling ergometer, and the other was a 10-min rest as a control. Range of motion (ROM) of ankle dorsiflexion, passive torque at terminal ROM, muscle-tendon unit (MTU) stiffness, muscle tendon junction displacement, peak torque of ankle plantarflexion, and the amplitude of electromyography (EMG) were measured. Immediately after the SS, in both interventions, ROM, passive torque, and muscle tendon junction displacement increased significantly (p < 0.05), while MTU stiffness, peak torque, and the amplitude of EMG were significantly decreased (p < 0.05). After 10-min on a cycling ergometer, the decreased peak torque and amplitude of EMG indicated higher values than those before SS (p < 0.05), while MTU stiffness was no change. In conclusion, SS increased ROM because of the decreased MTU stiffness as well as increased tolerance for stretching. Aerobic exercise could increase the muscle strength and amplitude of EMG which decreased after static stretching.