Model-informed drug development of envafolimab, a subcutaneously injectable PD-L1 antibody, in patients with advanced solid tumors.

BACKGROUND AND OBJECTIVES: Envafolimab is the first and only globally approved subcutaneously injectable PD-L1 antibody for the treatment of instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) advanced solid tumors in adults, including those with advanced colorectal cancer that has progressed after treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. The aim of this investigation was to examine the pharmacokinetic and exposure-response (E-R) profile of envafolimab in patients with solid tumors to support the approval of fixed and alternative dose regimens. METHODS: In this study, a population pharmacokinetic (PopPK) modeling approach will be employed to quantitatively evaluate intrinsic and extrinsic covariates. Additionally, PopPK-estimated exposure parameters were used to evaluate E-R relationship for safety and efficacy to provide a theoretical basis for recommending optimal treatment regimens. Simulations were performed on the dosing regimens of body weight-based regimen of 2.50 mg/kg QW, fixed dose 150 mg QW, and 300 mg Q2W for the selection of alternative dosing regimens. Data from 4 clinical studies (NCT02827968, NCT03101488, NCT03248843, and NCT03667170) were utilized. RESULTS: The PopPK dataset comprised 182 patients with 1810 evaluable envafolimab concentration records. Finally, a one-compartment model incorporating first-order absorption, first-order linear elimination, and time-dependent elimination according to an Emax function was found to accurately describe the concentration-time data of envafolimab in patients with advanced solid tumors. Creatinine clearance and country were identified as statistically significant factors affecting clearance, but had limited clinical significance. A relative flat exposure-response relationship was observed between early measures of safety and efficacy to verify that no dose adjustment is required. Simulation results indicated that 2.50 mg/kg QW, 150 mg QW, and 300 mg Q2W regimen yield similar steady-state exposure. CONCLUSIONS: No statistically significant difference was observed between weight-based and fixed dose regimens. Model-based simulation supports the adoption of a 150 mg weekly or 300 mg biweekly dosing regimen of envafolimab in the solid tumor population, as these schedules effectively balance survival benefits and safety risks.

Expedient access to polysubstituted acrylamides via strain-release-driven dual phosphine and palladium catalysis.

Polysubstituted acrylamides are ubiquitous in bioactive molecules and natural products. However, synthetic methods for the assembly of these important motifs remain underdeveloped. Herein, we report the expedient synthesis of structurally diverse and synthetically challenging polysubstituted acrylamides from readily available aromatic amines, cyclopropenones (CpOs), and aryl halides via the synergistic merging of nucleophilic phosphine-mediated amidation and palladium-catalyzed C-H arylation. The reaction is scalable, and some obtained acrylamides proved to be solid state luminogens with obvious aggregation-induced emission (AIE) properties, demonstrating the synthetic potential in drug discovery and material development.

Limited effects of xylem anatomy on embolism resistance in cycad leaves.

Drought-induced xylem embolism is a primary cause of plant mortality. Although c. 70% of cycads are threatened by extinction and extant cycads diversified during a period of increasing aridification, the vulnerability of cycads to embolism spread has been overlooked. We quantified the vulnerability to drought-induced embolism, pressure-volume curves, in situ water potentials, and a suite of xylem anatomical traits of leaf pinnae and rachises for 20 cycad species. We tested whether anatomical traits were linked to hydraulic safety in cycads. Compared with other major vascular plant clades, cycads exhibited similar embolism resistance to angiosperms and pteridophytes but were more vulnerable to embolism than noncycad gymnosperms. All 20 cycads had both tracheids and vessels, the proportions of which were unrelated to embolism resistance. Only vessel pit membrane fraction was positively correlated to embolism resistance, contrary to angiosperms. Water potential at turgor loss was significantly correlated to embolism resistance among cycads. Our results show that cycads exhibit low resistance to xylem embolism and that xylem anatomical traits - particularly vessels - may influence embolism resistance together with tracheids. This study highlights the importance of understanding the mechanisms of drought resistance in evolutionarily unique and threatened lineages like the cycads.

Investigation of Structures, Stabilities, and Electronic and Magnetic Properties of Niobium Carbon Clusters Nb7Cn (n = 1-7).

The geometrical structures, relative stabilities, and electronic and magnetic properties of niobium carbon clusters, Nb7Cn (n = 1-7), are investigated in this study. Density functional theory (DFT) calculations, coupled with the Saunders Kick global search, are conducted to explore the structural properties of Nb7Cn (n = 1-7). The results regarding the average binding energy, second-order difference energy, dissociation energy, HOMO-LUMO gap, and chemical hardness highlight the robust stability of Nb7C3. Analysis of the density of states suggests that the molecular orbitals of Nb7Cn primarily consist of orbitals from the transition metal Nb, with minimal involvement of C atoms. Spin density and natural population analysis reveal that the total magnetic moment of Nb7Cn predominantly resides on the Nb atoms. The contribution of Nb atoms to the total magnetic moment stems mainly from the 4d orbital, followed by the 5p, 5s, and 6s orbitals.

Application Effect of Graded Emergency Nursing in Patients with Acute Pancreatitis.

Background: Acute pancreatitis poses a significant threat in the emergency department due to its rapid and dangerous progression. Without timely and effective treatment measures, there is a heightened risk of advancing to multiple organ failure, posing a serious threat to the life safety of patients. Objective: This study aims to investigate the impact of graded emergency nursing on patients with acute pancreatitis. Design: A randomized controlled experiment was conducted to assess the effectiveness of graded emergency nursing. Setting: The study was conducted in the Emergency Department of Beijing Friendship Hospital, Capital University. Participants: A total of 112 patients diagnosed with acute pancreatitis and admitted to our hospital from June 2021 to December 2022 were randomly assigned to either the observation or control group, with 56 patients in each. Interventions: Patients in the control group received standard emergency nursing care, while those in the observation group underwent graded emergency nursing. Primary Outcome Measures: The study assessed (1) triage time, waiting time, and treatment time, (2) the correct rate of diagnosis and the success rate of rescue, (3) functional status score, and (4) patient satisfaction with nursing care. Results: Compared to the control group, patients in the observation group experienced significantly shorter triage time, waiting time, and treatment time (P < .05). Additionally, the observation group exhibited higher correct rates of diagnosis and success rates of rescue (P < .05). The functional status score in the observation group showed improvement (P < .05), and patients in the observation group reported higher satisfaction with nursing care (P < .05). Conclusions: Graded emergency nursing proves effective in reducing waiting times for diagnosis and treatment in acute pancreatitis patients, enhancing treatment success rates, and improving overall nursing quality. These findings hold valuable implications for clinical application and promotion.

Diagnostic Significance of Ultrasound-Guided Fine-Needle Aspiration Biopsy and on-Site Assessment by Pathologists for Thyroid Micronodules.

Objective: Ultrasound-guided fine-needle aspiration biopsy (US-FNAB) is a safe and effective method for screening malignant thyroid nodules. The purpose of this study was to compare the diagnostic effectiveness of US-FNAB for nodules of different sizes. Methods: A total of 1085 patients with thyroid nodules who underwent US-FNAB between January 2021 and July 2023 were included in the study. The patients were divided into three groups based on the maximum diameter of the nodules: there were 324 patients with thyroid nodules ≤5 mm in Group A, 537 patients with thyroid nodules between 6 mm and 10 mm in Group B, and 224 patients with thyroid nodules >10 mm in Group C. The US-FNAB satisfactory specimen rate, biopsy time and cytopathological results for the three groups were collected and compared with the postoperative pathological results. Results: The US-FNAB satisfactory specimen rates for Groups A, B and C were 84.57% (274/324), 90.13% (484/537) and 94.64% (212/224), respectively. The average biopsy times for Groups A, B, and C were 100.84 ± 41.58 s, 91.20 ± 32.53 s, and 79.01 ± 29.62 s, respectively. In Groups A, B, and C, 103, 192 and 73 patients, respectively, underwent surgery, and the malignancy rates were 88.35%, 85.42% and 72.6%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of US-FNAB in Group A were 78.26%, 81.82%, 97.30%, 31.03%; respectively; those in Group B were 73.78%,85.71%,96.80%, and 35.82%, respectively; and those in Group C were 75.47%, 85.00%, 93.02% and 56.67%, respectively. Conclusion: The US-FNAB satisfactory specimen rate for thyroid nodules ≤5 mm was relatively low, but the size of nodules had no effect on the diagnostic sensitivity of US-FNAB; additionally, nodules ≤5 mm had a higher probability of malignancy. Therefore, it is necessary to perform US-FNAB for thyroid nodules with a diameter ≤5 mm with malignant signs.

Aromatic and magnetic properties in a series of heavy rare earth-doped Ge6 cluster anions.

A series of pentagonal bipyramidal anionic germanium clusters doped with heavy rare earth elements, REGe 6 - (RE = Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu), have been identified at the PBE0/def2-TZVP level using density functional theory (DFT). Our findings reveal that the centrally doped pentagonal ring structure demonstrates enhanced stability and heightened aromaticity due to its uniform bonding characteristics and a larger charge transfer region. Through natural population analysis and spin density diagrams, we observed a monotonic decrease in the magnetic moment from Gd to Yb. This is attributed to the decreasing number of unpaired electrons in the 4f orbitals of the heavy rare earth atoms. Interestingly, the system doped with Er atoms showed lower stability and anti-aromaticity, likely due to the involvement of the 4f orbitals in bonding. Conversely, the systems doped with Gd and Tb atoms stood out for their high magnetism and stability, making them potential building blocks for rare earth-doped semiconductor materials.

Differential Characteristics of Fatigue-Pain-Sleep Disturbance-Depression Symptom Cluster and Influencing Factors of Patients With Advanced Cancer During Treatment: A Latent Class Analysis.

BACKGROUND: Patients with advanced cancer may experience symptom clusters during treatment (eg, fatigue, pain, sleep disturbance, depression). Understanding the characteristics and factors associated with symptom cluster classes among this patient population is essential for effective symptom management. OBJECTIVE: The aims of this study were to identify symptom cluster (fatigue-pain-sleep disturbance-depression) classes and explore influencing factors in patients with advanced cancer during the treatment. METHODS: A cross-sectional survey was conducted in an oncology department of a tertiary hospital in China from September 2020 to March 2021. Cancer patients (stage III/IV) 18 years or older completed the questionnaires on pain, fatigue, sleep disturbance, depression, physical activity, and exercise self-efficacy. Latent class analysis and multinomial logistic regression were used. RESULTS: Three hundred sixty-five patients who were male (65.2%) and younger than 60 years (59.5%) completed questionnaires. Three symptom cluster classes were identified: class 1 ("low symptom burden" class), class 2 ("fatigue-insomnia" class), and class 3 ("high symptom burden" class), with a percentage of 54.5%, 38.6%, and 6.8%, respectively. The quality-of-life score, introversion/extroversion, economic burden, Karnofsky Performance Status, albumin level, and exercise self-efficacy were significantly different among the 3 classes (P < .05). CONCLUSION: Patients with advanced cancer were classified into 3 distinct classes, with class 1 having the best function. Results from this study reveal that Karnofsky Performance Status, albumin level, and exercise self-efficacy were significant factors for the latent classes of symptom cluster. IMPLICATIONS FOR PRACTICE: Exercise self-efficacy is important for personalized interventions and improving symptom management efficiency.

Computer-assisted microcatheter shaping for intracranial aneurysm embolization: evaluation of safety and efficacy in a multicenter randomized controlled trial.

BACKGROUND: This study aimed to evaluate the efficacy, stability, and safety of computer-assisted microcatheter shaping (CAMS) in patients with intracranial aneurysms. METHODS: A total of 201 patients with intracranial aneurysms receiving endovascular coiling therapy were continuously recruited and randomly assigned to the CAMS and manual microcatheter shaping (MMS) groups. The investigated outcomes included the first-trial success rate, time to position the microcatheter in aneurysms, rate of successful microcatheter placement within 5 min, delivery times, microcatheter stability, and delivery performance. RESULTS: The rates of first-trial success (96.0% vs 66.0%, P<0.001), successful microcatheter placement within 5 min (96.04% vs 72.00%, P<0.001), microcatheter stability (97.03% vs 84.00%, P=0.002), and 'excellent' delivery performance (45.54% vs 24.00%, P<0.001) in the CAMS group were significantly higher than those in the MMS group. Additionally, the total microcatheter delivery and positioning time (1.05 minutes (0.26) vs 1.53 minutes (1.00)) was significantly shorter in the CAMS group than in the MMS group (P<0.001). Computer assistance (OR 14.464; 95% CI 4.733 to 44.207; P<0.001) and inflow angle (OR 1.014; 95% CI 1.002 to 1.025; P=0.021) were independent predictors of the first-trial success rate. CAMS could decrease the time of microcatheter position compared with MMS, whether for junior or senior surgeons (P<0.001). Moreover, computer assistance technology may be more helpful in treating aneurysms with acute angles (p<0.001). CONCLUSIONS: The use of computer-assisted procedures can enhance the efficacy, stability, and safety of surgical plans for coiling intracranial aneurysms.

Case Report: A combination of chimeric CYP11B2/CYP11B1 and a novel p.Val68Gly CYP11B1 variant causing 11ß-Hydroxylase deficiency in a Chinese patient.

Introduction: 11ß-Hydroxylase deficiency (11ß-OHD, OMIM#202010) is the second most common form of congenital adrenal hyperplasia (CAH) caused by pathogenic variants in the CYP11B1 gene. Both single nucleotide variations (SNV)/small insertion and deletion and genomic rearrangements of CYP11B1 are important causes of 11ß-OHD. Among these variant types, pathogenic CYP11B2/CYP11B1 chimeras only contribute to a minority of cases. Heterozygote cases (chimera combined with SNV) are very rare, and genetic analysis of these cases can be challenging. Case presentation: We presented a suspected 11ß-OHD female patient with incomplete virilization, adrenal hyperplasia, and hypokalemia hypertension. Whole exome sequencing (WES) revealed that the patient carried both a chimeric CYP11B2/CYP11B1 and a novel missense variant, NM_000497.4: c.203T>G, p.Val68Gly (chr8:143961027) in CYP11B1, which were confirmed by CNVplex and Sanger sequencing, respectively. The patient's manifestations and genetic findings confirmed the diagnosis of 11ß-OHD, and oral dexamethasone was administered as a subsequent treatment. Conclusion: This report showed a rare CYP11B2/CYP11B1 chimera combined with a novel missense variant in a 11ß-OHD female patient. The result expands variant spectrum of CYP11B1 and suggests that both chimera and CYP11B1 variant screening should be performed simultaneously in suspected cases of 11ß-OHD. To our knowledge, this is the first report about CYP11B2/CYP11B1 chimera detected by WES analysis. WES combined with CNV analysis is an efficient method in the genetic diagnosis of this rare and complex disorder.

Treatment of posterior interosseous nerve entrapment syndrome with ultrasound-guided hydrodissection: A case report.

BACKGROUND: Posterior interosseous nerve (PIN) entrapment syndrome is one of the causes of weakness and pain of the arm muscles, which is prone to missed diagnosis and misdiagnosis in clinic practice. This paper reports a case of PIN entrapment syndrome, with PIN injury indicated by electrophysiology. Musculoskeletal ultrasound was applied to identify that the entrapment point was located at the inlet of the Frohse arch and the outlet of the supinator muscle. Treatment with ultrasound-guided nerve hydrodissection was performed on the entrapment point, which significantly improved the symptoms. Ultrasound-guided nerve hydrodissection is an effective therapeutic method for PIN entrapment syndrome. CASE SUMMARY: A male patient, 35 years old, worked as an automobile mechanic. He felt slightly weak extension activity of his right fingers 2 years ago but sought no treatment. Later, the symptoms gradually became aggravated and led to finger drop, particularly severe in the right middle finger, accompanied by supination weakness of the right forearm. Neural electrophysiological examination showed that the patient had partial PIN injury of the right radius. Musculoskeletal ultrasound examination indicated PIN entrapment at the inlet of the Frohse arch and the outlet of the supinator muscle. Therefore, PIN entrapment syndrome was diagnosed. After treatment with ultrasound-guided nerve hydrodissection around the entrapment point, the dorsiflexion weakness of the right hand was significantly improved compared with before treatment. CONCLUSION: Ultrasound-guided hydrodissection is efficacious for PIN entrapment syndrome, with high clinical value and great application prospects.

Making Sense of the Growth Behavior of Ultra-High Magnetic Gd2-Doped Silicon Clusters.

The growth behavior, stability, electronic and magnetic properties of the Gd2Sin- (n = 3-12) clusters are reported, which are investigated using density functional theory calculations combined with the Saunders 'Kick' and the Artificial Bee Colony algorithm. The lowest-lying structures of Gd2Sin- (n = 3-12) are all exohedral structures with two Gd atoms face-capping the Sin frameworks. Results show that the pentagonal bipyramid (PB) shape is the basic framework for the nascent growth process of the present clusters, and forming the PB structure begins with n = 5. The Gd2Si5- is the potential magic cluster due to significantly higher average binding energies and second order difference energies, which can also be further verified by localized orbital locator and adaptive natural density partitioning methods. Moreover, the localized f-electron can be observed by natural atomic orbital analysis, implying that these electrons are not affected by the pure silicon atoms and scarcely participate in bonding. Hence, the implantation of these elements into a silicon substrate could present a potential alternative strategy for designing and synthesizing rare earth magnetic silicon-based materials.

MicroRNA-1179 targets Epiregulin (EREG) regulates the proliferation and metastasis of human multiple myeloma cells.

MicroRNA-1179 (miRNA-1179) is an extensively studied tumor suppressor. however, the significance of miR-1179 in multiple myeloma has not been investigated previously. So, there is a need for research to find out about the significance of miR-1179 in multiple myeloma. However, current investigations have examined the significance of miRNA-1179 in multiple myeloma for the first time by targeting epiregulin (EREG). In this study, 26 multiple myeloma specimens and 16 healthy donor specimens were examined. Multiple myeloma cell lines (U266, RPMI-8226, KMS-11, JJN-3, and IM-9) were used. In this study, expression analysis, cell viability, colony formation assay, and transwell assay were carried out by standard methods. The outcomes revealed the downregulation of miRNA-1179 in multiple myeloma. Overexpression of miRNA-1179 promotes, while its inhibition suppresses, the survival ability and colony formation of the U266 multiple myeloma cells. Investigation of underlying mechanisms revealed apoptosis to be responsible for the tumour-suppressive effects of miRNA-1179. The proportion of apoptosis in U266 cells rose from 5.32% to 34.86% when miRNA-1179 was overexpressed. Additionally, it was discovered that miRNA-1179 directs its tumor-inhabiting activities toward EREG at the molecular level. While EREG knockdown was found to halt the proliferation of U266 cells, its overexpression could overcome the suppressive effects of miRNA-1179 on the survival ability, mobility, and invasion of the U266 cells. This research proves that miRNA-1179 can be used as a new treatment or drug for multiple myeloma.

Preparation of Fe/Ni-MOFs for the Adsorption of Ciprofloxacin from Wastewater.

This work studies the use of Fe/Ni-MOFs for the removal of ciprofloxacin (CIP) in wastewater. Fe/Ni-MOFs are prepared by the solvothermal method and characterized by X-ray diffraction (XRD), a scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR), and a thermal gravimetric analyzer (TG). Under the conditions of the concentration of 50 ppm, a mass of 30 mg, and a temperature of 30 °C, the maximum adsorption capacity of ciprofloxacin removal within 5 h was 232.1 mg/g. The maximum removal rate was 94.8% when 40 mg of the Fe/Ni-MOFs was added to the solution of 10 ppm ciprofloxacin. According to the pseudo-second-order (PSO) kinetic model, the R2 values were all greater than 0.99, which proved that the adsorption theory of ciprofloxacin by Fe/Ni-MOFs was consistent with the practice. The adsorption results were mainly affected by solution pH and static electricity, as well as other factors. The Freundlich isotherm model characterized the adsorption of ciprofloxacin by Fe/Ni-MOFs as multilayer adsorption. The above results indicated that Fe/Ni-MOFs were effective in the practical application of ciprofloxacin removal.

N-doped carbon dots coupled with molecularly imprinted polymers as a fluorescent sensor for ultrasensitive detection of genistein in soya products.

Rapid detection of genistein in soya products has remained difficult. Current methods necessitate sample handling and use of costly instruments. Here, using a simple one-pot reverse microemulsion method, a sensor based on N-doped carbon dots conjugated molecularly imprinted polymers (N-CDs@MIPs) was synthesized to analyze genistein. N-doped carbon dots were used as fluorescent component, genistein as the template molecule, and molecularly imprinted polymers as the selective sorbent in this fluorescence sensor. The sensor was then examined and optical studies demonstrated that N-CDs@MIPs not only had strong fluorescence emission and outstanding optical stability, but also had good sensitivity (detection limit 35.7 nM) and selectivity to genistein. Furthermore, the N-CDs@MIPs materials were used to analyze genistein in soya products, and the findings (which ranged from 99.77% to 106.11%) show that the N-CDs@MIPs has high potential for quickly detecting the amount of genistein in complicated food samples.

Coordination of intertracheid pit traits and climate effects among cycads.

Interconduit pit membranes, which are permeable regions in the primary cell wall that connect to adjacent conduits, play a crucial role in water relations and the movement of nutrients between xylem conduits. However, how pit membrane characteristics might influence water-carbon coupling remains poorly investigated in cycads. We examined pit characteristics, the anatomical and photosynthetic traits of 13 cycads from a common garden, to determine if pit traits and their coordination are related to water relations and carbon economy. We found that the pit traits of cycads were highly variable and that cycads exhibited a similar tradeoff between pit density and pit area as other plant lineages. Unlike other plant lineages (1) pit membranes, pit apertures, and pit shapes of cycads were not coordinated as in angiosperms; (2) cycads exhibited larger pit membrane areas but lower pit densities relative to ferns and angiosperms, but smaller and similar pit membrane densities to non-cycad gymnosperms; (3) cycad pit membrane areas and densities were partially coordinated with anatomical traits, with hydraulic supply of the rachis positively coordinated with photosynthesis, whereas pit aperture areas and fractions were negatively coordinated with photosynthetic traits; (4) cycad pit traits reflected adaptation to wetter habitats for Cycadaceae and drier habitats for Zamiaceae. The large variation in pit traits, the unique pit membrane size and density, and the partial coordination of pit traits with anatomical and physiological traits of the rachis and pinna among cycads may have facilitated their dominance in a variety of ecosystems from the Mesozoic to modern times.

Case Report: Identification of a novel NTRK3-AJUBA fusion co-existing with ETV6-NTRK3 fusion in papillary thyroid carcinoma.

NTRK fusions are validated oncogenic drivers of various adult and pediatric tumor types, including thyroid cancer, and serve as a therapeutic target. Recently, tropomyosin receptor kinase (TRK) inhibitors, such as entrectinib and larotrectinib, display promising therapeutic efficacy in NTRK-positive solid tumors. Although some NTRK fusion partners have been identified in thyroid cancer, the spectrum of NTRK fusion is not fully characterized. In this study, a dual NTRK3 fusion was identified by targeted RNA-Seq in a 47-year-old female patient with papillary thyroid carcinoma. The patient harbors a novel in-frame fusion between NTRK3 exon 13 and AJUBA exon 2, co-existing with a known in-frame fusion between ETV6 exon 4 and NTRK3 exon 14. The dual NTRK3 fusion was validated by Sanger sequencing and fluorescence in situ hybridization (FISH) but lack TRK protein expression as defined by pan-TRK immunohistochemistry (IHC). We supposed the pan-TRK IHC result to be falsely negative. In conclusion, we present the first case of a novel NTRK3-AJUBA fusion co-existing with a known ETV6-NTRK3 fusion in thyroid cancer. These findings extend the spectrum of translocation partners in NTRK3 fusion, and the effect of dual NTRK3 fusion on TRK inhibitor therapy and prognosis needs long-term follow-up.

Comprehensive Bibliometric Analysis of Stem Cell Research in Alzheimer's Disease from 2004 to 2022.

INTRODUCTION: Stem cell-based regenerative medicine has provided an excellent opportunity to investigate therapeutic strategies and innovative treatments for Alzheimer's disease (AD). However, there is an absence of visual overviews to assess the published literature systematically. METHODS: In this review, the bibliometric approach was used to estimate the searched data on stem cell research in AD from 2004 to 2022, and we also utilized CiteSpace and VOSviewer software to evaluate the contributions and co-occurrence relationships of different countries/regions, institutes, journals, and authors as well as to discover research hot spots and encouraging future trends in this field. RESULTS: From 2004 to 2022, a total of 3,428 publications were retrieved. The number of publications and citations on stem cell research in AD has increased dramatically in the last nearly 20 years, especially since 2016. North America and Asia were the top 2 highest output regions. The leading country in terms of publications and access to collaborative networks was the USA. Centrality analysis revealed that the UCL (0.05) was at the core of the network. The Journal of Alzheimer's Disease (n = 102, 2.98%) was the most productive academic journal. The analyses of keyword burst detection indicated that exosomes, risk factors, and drug delivery only had burst recently. Citations and co-citation achievements clarified that cluster #0 induced pluripotent stem cells, #2 mesenchymal stem cells, #3 microglia, and #6 adult hippocampal neurogenesis persisted to recent time. CONCLUSION: This bibliometric analysis provides a comprehensive guide for clinicians and scholars working in this field. These analysis and results hope to provide useful information and references for future understanding of the challenges behind translating underlying stem cell biology into novel clinical therapeutic potential in AD.

Evaluation of Solubility, Physicochemical Properties, and Cytotoxicity of Naproxen-Based Ionic Liquids.

To solve the problems associated with poorly water-soluble nonsteroidal anti-inflammatory drugs (NSAIDs), naproxen-based ionic liquids (ILs) containing naproxen as an active pharmaceutical ingredient (API) anion were prepared with benzalkonium (tetradecyldimethylbenzyl ammonium), choline, and 1-octyl-3-methylimidazole as the cation. The structures and thermal properties were analyzed. Through the conductivity method, the solubility at 25 and 37 °C and the critical micelle concentration (CMC) at 25 °C were determined in water and ethanol. The octanol-water partition coefficients (K ow) at 25 °C were measured with the shake-flask method. The cytotoxicity was evaluated with the MTT method. The results showed that the conversion of naproxen into the API-ILs increased the API's solubility in water by more than 850 times compared with the original API, and the thermostability was satisfactory with a lower glass transition temperature (t g). Moreover, the variation trends of solubility, hydrophilicity, and K ow were consistent with the different structures of naproxen-based ILs, except for benzalkonium naproxen. The CMC (10-5-10-6 M) in water and ethanol demonstrated that the naproxen-based ILs were surface activite ILs. The IC50 values exhibited the low cytotoxicity of the naproxen-based ILs, which was better than 100 µM. The results provide essential information and a research basis for future topical and transdermal administration and oral administration of naproxen-based ILs.

Structural Regulation of Two Polyoxometalate-Based Metal-Organic Frameworks for the Heterogeneous Catalysis of Quinazolinones.

Two dimeric {ε-Zn4PMo12}-based metal-organic frameworks (MOFs), [ε-PMo8VMo4VIO34(OH)6Zn4][LO] (SDUT-21, LO = [5-((4'-carboxybenzyl)oxy)isophthalic acid]) and [TBA]3[ε-PMo8VMo4VIO37(OH)3Zn4][LN] (SDUT-22, TBA+ = tetrabutylammonium ion, LN = [5-((4-carboxybenzyl)imino)isophthalic acid]), combining the advantages of polyoxometalates (POMs) and MOFs, were synthesized by the one-pot assembly strategy. The dimeric {ε-Zn4PMo12} units act as nodes that are linked by the flexible ligands and extended into two- or three-dimensional frameworks. The cyclic voltammetry and proton conductivity measurements of SDUT-21 and SDUT-22 were performed and indicated the high electron and proton transfer abilities. These materials also e xhibited the catalytic performance for the synthesis of quinazolinones in the heterogeneous state, and the different binding capacities toward the substrates caused the catalytic activity of SDUT-21 to be higher than that of SDUT-22 under the same conditions. In addition, the used catalysts could be readily recovered for five successive cycles and maintained high catalytic efficiency.