Harnessing instability for work hardening in multi-principal element alloys.

The strength-ductility trade-off has long been a Gordian knot in conventional metallic structural materials and it is no exception in multi-principal element alloys. In particular, at ultrahigh yield strengths, plastic instability, that is, necking, happens prematurely, because of which ductility almost entirely disappears. This is due to the growing difficulty in the production and accumulation of dislocations from the very beginning of tensile deformation that renders the conventional dislocation hardening insufficient. Here we propose that premature necking can be harnessed for work hardening in a VCoNi multi-principal element alloy. Lüders banding as an initial tensile response induces the ongoing localized necking at the band front to produce both triaxial stress and strain gradient, which enables the rapid multiplication of dislocations. This leads to forest dislocation hardening, plus extra work hardening due to the interaction of dislocations with the local-chemical-order regions. The dual work hardening combines to restrain and stabilize the premature necking in reverse as well as to facilitate uniform deformation. Consequently, a superior strength-and-ductility synergy is achieved with a ductility of ~20% and yield strength of 2 GPa during room-temperature and cryogenic deformation. These findings offer an instability-control paradigm for synergistic work hardening to conquer the strength-ductility paradox at ultrahigh yield strengths.

Further delineation of phenotype and genotype of Kenny-Caffey syndrome type 2 (phenotype and genotype of KCS type 2).

BACKGROUND: Kenny-Caffey syndrome type 2 (KCS2) is an extremely rare inherited disorder characterized by proportionate short stature, skeletal defects, ocular and dental abnormalities, and transient hypocalcemia. It is caused by variants in FAM111A gene. Diagnosis of KCS2 can be challenging because of its similarities to other syndromes, the absence of clear hallmarks and the deficient number of genetically confirmed cases. Here, we aimed to further delineate and summarize the genotype and phenotype of KCS2, in order to get a better understanding of this rare disorder, and promote early diagnosis and intervention. METHODS: We present clinical and genetic characteristics of eight newly affected individuals with KCS2 from six families, including one family with three individuals found to be a father-to-daughter transmission, adding to the limited literature. Furthermore, we performed a review of genetically confirmed KCS2 cases in PubMed, MEDLINE and CNKI databases. RESULTS: There were six females and two males in our cohort. All the patients presented with short stature (100.0%). Clinical manifestations included ocular defects such as hypermetropia (5/8), dental problems such as defective dentition (3/8) and dental caries (3/8), skeletal and brain anomalies such as delayed closure of anterior fontanelle (6/8), cerebral calcification (3/8), cortical thickening (3/8) and medullary stenosis (4/8) of tubular bones. Endocrinologic abnormalities included hypoparathyroidism (5/8) and hypocalcemia (3/8). One male patient had micropenis and microorchidism. All cases harboured missense variants of FAM111A, and nucleotides c.1706 arose as a mutational hotspot, with seven individuals harbouring a c.1706G>A (p.Arg569His) variant, and one child harbouring a c.1531T>C (p.Tyr511His) variant. Literature review yielded a total of 46 patients from 20 papers. Data analysis showed that short stature, hypoparathyroidism and hypocalcemia, ocular and dental defects, skeletal features including cortical thickening and medullary stenosis of tubular bones, and seizures/spasms were present in more than 70% of the reported KCS2 cases. CONCLUSION: We provide detailed characteristics of the largest KCS2 group in China and present the first genetically confirmed instance of father-to-daughter transmission of KCS2. Our study confirms that Arg569His is the hot spot variant and summarizes the typical phenotypes of KCS2, which would help early diagnosis and intervention.

Targeted Liposomes Sensitize Plastic Melanoma to Ferroptosis via Senescence Induction and Coenzyme Depletion.

Ferroptotic cancer therapy has been extensively investigated since the genesis of the ferroptosis concept. However, the therapeutic efficacy of ferroptosis induction in heterogeneous and plastic melanoma has been compromised, because the melanocytic and transitory cell subpopulation is resistant to iron-dependent oxidative stress. Here, we report a phenotype-altering liposomal nanomedicine to enable the ferroptosis-resistant subtypes of melanoma cells vulnerable to lipid peroxidation via senescence induction. The strategy involves the ratiometric coencapsulation of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor (palbociclib) and a ferroptosis inducer (auranofin) within cRGD peptide-modified targeted liposomes. The two drugs showed a synergistic anticancer effect in the model B16F10 melanoma cells, as evidenced by the combination index analysis (<1). The liposomes could efficiently deliver both drugs into B16F10 cells in a targeted manner. Afterward, the liposomes potently induced the intracellular redox imbalance and lipid peroxidation. Palbociclib significantly provoked cell cycle arrest at the G0/G1 phase, which sensitized auranofin-caused ferroptosis through senescence induction. Meanwhile, palbociclib depleted intracellular glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH), further boosting ferroptosis. The proof-of-concept was also demonstrated in the B16F10 tumor-bearing mice model. The current work offers a promising ferroptosis-targeting strategy for effectively treating heterogeneous melanoma by manipulating the cellular plasticity.

Lactate coordinated with exercise promoted the browning of inguinal white adipose tissue.

Lactate, an important exercise metabolite, induces white adipose tissue browning by upregulated uncoupling protein 1 (UCP1) expression. However, the function of lactate during browning of inguinal white adipose tissue (iWAT) caused by exercise is unclear. Here, we considered lactate as an exercise supplement and investigated the effects of chronic pre-exercise lactate administration on energy metabolism and adipose tissue browning. C57B/L6 male mice (5 weeks of age) were divided into six groups. We evaluated the changes in blood lactate levels in each group of mice after the intervention. Energy expenditure was measured after the intervention immediately by indirect calorimetry. The marker protein levels and gene expressions were determined by western-blot and quantitative real-time PCR. HIIT significantly decreased adipose tissue weight while increased energy expenditure and the expression of UCP1 in iWAT; however, these regulations were inhibited in the DCA+HIIT group. Compared with the MICT and LAC groups, long-term lactate injection before MICT led to lower WAT weight to body weight ratios and higher energy expenditure in mice. Furthermore, the marker genes of browning in iWAT, such as Ucp1 and Pparγ, were significantly increased in the LAC+MICT group than in the other groups, and the expression of monocarboxylate transporter-1 (Mct1) mRNA was also significantly increased. Lactate was involved in exercise-mediated browning of iWAT, and its mechanism might be the increased of lactate transport through MCT1 or PPARγ upregulation induced by exercise. These findings suggest exogenous lactate may be a new exercise supplement to regulate metabolism.

Deep insights into biodegradability mechanism and growth cycle adaptability of polylactic acid/hyperbranched cellulose nanocrystal composite mulch.

The widespread use of petroleum-based plastic mulch in agriculture has accelerated white and microplastic pollution while posing a severe agroecological challenge due to its difficulty in decomposing in the natural environment. However, endowing mulch film with degradability and growth cycle adaptation remains elusive due to the inherent non-degradability of petroleum-based plastics severely hindering its applications. This work reports polylactic acids hyperbranched composite mulch (PCP) and measured biodegradation behavior under burial soil, seawater, and ultraviolet (UV) aging to understand the biodegradation kinetics and to increase their sustainability in the agriculture field. Due to high interfacial interactions between polymer and nanofiler, the resultant PCP mulch significantly enhances crystallization ability, hydrophilicity, and mechanical properties. PCP mulch can be scalable-manufactured to exhibit modulated degradation performance under varying degradation conditions and periods while concurrently enhancing crop growth (wheat). Thus, such mulch with excellent performance can reduce labor costs and the environmental impact of waste mulch disposal to replace traditional mulch for sustainable agricultural production.

Reversing Ferroptosis Resistance in Breast Cancer via Tailored Lipid and Iron Presentation.

Ferroptotic cancer therapy is promising in many scenarios where traditional cancer therapies show a poor response. However, certain types of cancers lack the long-chain acyl-CoA synthetase 4 (ACSL4), a key modulator of ferroptosis, resulting in therapy resistance and tumor relapse. Because ACSL4 is in charge of the synthesis of ferroptotic lipids (e.g., arachidonoylphosphatidylethanolamine/PE-AA), we postulated that direct delivery of PE-AA may reverse ferroptosis resistance induced by ACSL4 deficiency. To further increase the ferroptosis sensitivity, we employed the ferrocene-bearing polymer micelles to co-load PE-AA with an FDA-approved redox modulator, auranofin (Aur), targeting the thioredoxin reductase. The presence of ferrocene enabled triggered cargo release and iron production, which can sensitize ferroptosis by boosting autoxidation-mediated PE-AA peroxidation. The micellar system could impair redox homeostasis and induce lipid peroxidation in ACSL4-deficient MCF-7 cells. Moreover, the tailored micelles potently induced ferroptosis in MCF-7 tumors in vivo, suppressed tumor growth, and increased the mice's survival rate. The current work provides a facile means for reversing the ferroptosis resistance in ACSL4-deficient tumors.

Lessons from assembling a microbial natural product and pre-fractionated extract library in an academic laboratory.

Microbial natural products are specialized metabolites that are sources of many bioactive compounds including antibiotics, antifungals, antiparasitics, anticancer agents, and probes of biology. The assembly of libraries of producers of natural products has traditionally been the province of the pharmaceutical industry. This sector has gathered significant historical collections of bacteria and fungi to identify new drug leads with outstanding outcomes-upwards of 60% of drug scaffolds originate from such libraries. Despite this success, the repeated rediscovery of known compounds and the resultant diminishing chemical novelty contributed to a pivot from this source of bioactive compounds toward more tractable synthetic compounds in the drug industry. The advent of advanced mass spectrometry tools, along with rapid whole genome sequencing and in silico identification of biosynthetic gene clusters that encode the machinery necessary for the synthesis of specialized metabolites, offers the opportunity to revisit microbial natural product libraries with renewed vigor. Assembling a suitable library of microbes and extracts for screening requires the investment of resources and the development of methods that have customarily been the proprietary purview of large pharmaceutical companies. Here, we report a perspective on our efforts to assemble a library of natural product-producing microbes and the establishment of methods to extract and fractionate bioactive compounds using resources available to most academic labs. We validate the library and approach through a series of screens for antimicrobial and cytotoxic agents. This work serves as a blueprint for establishing libraries of microbial natural product producers and bioactive extract fractions suitable for screens of bioactive compounds. ONE-SENTENCE SUMMARY: Natural products are key to discovery of novel antimicrobial agents: Here, we describe our experience and lessons learned in constructing a microbial natural product and pre-fractionated extract library.

Effect of Anisotropic Structural Depth on Orientation and Differentiation Behavior of Skeletal Muscle Cells.

Extensive research has been conducted to examine how substrate topological factors are involved in modulating the cell behavior. Among numerous topological factors, the vital influence of the touchable depth of substrates on cell behaviors has already been extensively characterized, but the response of cells to the topological structure at untouchable depth is still elusive. Herein, the influences of substrate depth on myoblast behaviors are systematically investigated using substrates with depths ranging from touchable depth (microgrooved) to untouchable depth (microbridges). The results show that an increase in microgroove depth is accompanied by an inhibited cell spreading, an enhanced elongation, and a more obvious orientation along microgrooves. Interestingly, myoblasts located on microbridges show a more pronounced elongation with increasing culture time but a position-dependent orientation. Myoblasts on the center and parallel boundary of microbridges orient along the bridges, while myoblasts on the vertical boundary align perpendicular to the microbridges. Moreover, the differentiation results of the myoblasts indicate that the differentiated myotubes can maintain this position-dependent orientation. The simulation of the stress field in cell monolayers suggests that the position-dependent orientation is caused by the comprehensive response of myoblasts to the substrate discontinuity and substrate depth. These findings provide valuable insights into the mechanism of cell depth sensing and could inform the design of tissue engineering scaffolds for skeletal muscle and biohybrid actuation.

Two Different Isocitrate Dehydrogenases from Pseudomonas aeruginosa: Enzymology and Coenzyme-Evolutionary Implications.

Pseudomonas aeruginosa PAO1, as an experimental model for Gram-negative bacteria, harbors two NADP+-dependent isocitrate dehydrogenases (NADP-IDHs) that were evolved from its ancient counterpart NAD-IDHs. For a better understanding of PaIDH1 and PaIDH2, we cloned the genes, overexpressed them in Escherichia coli and purified them to homogeneity. PaIDH1 displayed higher affinity to NADP+ and isocitrate, with lower Km values when compared to PaIDH2. Moreover, PaIDH1 possessed higher temperature tolerance (50 °C) and wider pH range tolerance (7.2-8.5) and could be phosphorylated. After treatment with the bifunctional PaIDH kinase/phosphatase (PaIDH K/P), PaIDH1 lost 80% of its enzymatic activity in one hour due to the phosphorylation of Ser115. Small-molecule compounds like glyoxylic acid and oxaloacetate can effectively inhibit the activity of PaIDHs. The mutant PaIDH1-D346I347A353K393 exhibited enhanced affinity for NAD+ while it lost activity towards NADP+, and the Km value (7770.67 µM) of the mutant PaIDH2-L589 I600 for NADP+ was higher than that observed for NAD+ (5824.33 µM), indicating a shift in coenzyme specificity from NADP+ to NAD+ for both PaIDHs. The experiments demonstrated that the mutation did not alter the oligomeric state of either protein. This study provides a foundation for the elucidation of the evolution and function of two NADP-IDHs in the pathogenic bacterium P. aeruginosa.

High-intensity interval training induces lactylation of fatty acid synthase to inhibit lipid synthesis.

BACKGROUND: The aim of study was to observe the effect of increased lactate levels during high-intensity interval training (HIIT) on protein lactylation, identify the target protein, and investigate the regulatory effect of lactylation on the function of the protein. METHODS: C57B/L6 mice were divided into 3 groups: the control group, HIIT group, and dichloroacetate injection + HIIT group (DCA + HIIT). The HIIT and DCA + HIIT groups underwent 8 weeks of HIIT treatment, and the DCA + HIIT group was injected DCA before HIIT treatment. The expression of lipid metabolism-related genes was determined. Protein lactylation in subcutaneous adipose tissue was identified and analyzed using 4D label-free lactylation quantitative proteomics and bioinformatics analyses. The fatty acid synthase (FASN) lactylation and activity was determined. RESULTS: HIIT had a significant effect on fat loss; this effect was weakened when lactate production was inhibited. HIIT significantly upregulated the protein lactylation while lactate inhibition downregulated in iWAT. FASN had the most modification sites. Lactate treatment increased FASN lactylation levels, inhibited FASN activity, and reduced palmitate and triglyceride synthesis in 3T3-L1 cells. CONCLUSIONS: This investigation revealed that lactate produced by HIIT increased protein pan-lactylation levels in iWAT. FASN lactylation inhibited de novo lipogenesis, which may be an important mechanism in HIIT-induced fat loss.

Crosstalk between ABA and ethylene in regulating stomatal behavior in tomato under high CO2 and progressive soil drying.

Increasing atmospheric CO2 concentrations accompanied by intensifying drought markedly impact plant growth and physiology. This study aimed to explore the role of abscisic acid (ABA) in mediating the response of stomata to elevated CO2 (e[CO2]) and drought. Tomato plants with different endogenous ABA concentrations [Ailsa Craig (AC), the ABA-deficient mutant flacca, and ABA-overproducing transgenic tomato SP5] were grown in ambient (a[CO2], 400 µmol mol-1) and elevated (e[CO2],800 µmol mol-1) CO2 environments and subjected to progressive soil drying. Compared with a[CO2] plants, e[CO2] plants had significantly lower stomatal conductance in AC and SP5 but not in flacca. Under drought, e[CO2] plants had better water status and higher water use efficiency. e[CO2] promoted the accumulation of ABA in leaves of plants subjected to drought, which coincided with the up-regulation of ABA biosynthetic genes and down-regulation of ABA metabolic genes. Although the increase of ABA induced by drought in flacca was much less than in AC and SP5, flacca accumulated large amounts of ethylene, suggesting that in plants with ABA deficiency, ethylene might play a compensatory role in inducing stomatal closure during soil drying. Collectively, these findings improve our understanding of plant performance in a future drier and higher-CO2 environment.

Enzymatic Characterization of the Isocitrate Dehydrogenase with Dual Coenzyme Specificity from the Marine Bacterium Umbonibacter marinipuiceus.

Isocitrate dehydrogenase (IDH) can be divided into NAD+-dependent and NADP+-dependent types based on the coenzyme specificity. It is worth noting that some IDHs exhibit dual coenzyme specificity characteristics. Herein, a dual coenzyme-dependent IDH from Umbonibacter Marinipuiceus (UmIDH) was expressed, purified, and identified in detail for the first time. SDS-PAGE and Gel filtration chromatography analyses showed that UmIDH is an 84.7 kDa homodimer in solution. The Km values for NAD+ and NADP+ are 1800.0 ± 64.4 µM and 1167.7 ± 113.0 µM in the presence of Mn2+, respectively. Meanwhile, the catalytic efficiency (kcat/Km) of UmIDH is only 2.3-fold greater for NADP+ than NAD+. The maximal activity for UmIDH occurred at pH 8.5 (with Mn2+) or pH 8.7 (with Mg2+) and at 35 °C (with Mn2+ or Mg2+). Heat inactivation assay revealed that UmIDH sustained 50% of maximal activity after incubation at 57 °C for 20 min with either Mn2+ or Mg2+. Moreover, three putative core coenzyme binding residues (R345, L346, and V352) of UmIDH were evaluated by site-directed mutagenesis. This recent work identified a unique dual coenzyme-dependent IDH and achieved the groundbreaking bidirectional modification of this specific IDH's coenzyme dependence for the first time. This provides not only a reference for the study of dual coenzyme-dependent IDH, but also a basis for the investigation of the coenzyme-specific evolutionary mechanisms of IDH.

In vitro remineralization assessment of enamel subsurface lesions using different percentages of surface reaction-type pre-reacted glass-ionomer containing gum-based material.

OBJECTIVE: To identify the remineralization activity of enamel subsurface lesions using different percentages of surface pre-reacted glass-ionomer (S-PRG) filler containing gum-base material. METHODS: Gum extracts from gum-base materials containing 0wt%, 5wt%, and 10wt% S-PRG filler were prepared as GE0, GE5, and GE10, respectively. A total of 50 bovine enamel specimens were used, and the polished enamel surface of a 3 × 3 mm2 window area was exposed. The specimens were then subjected to a demineralization solution for seven days to create a subsurface enamel lesion. Remineralization was then conducted for seven days using a protocol whereby the specimens were immersed three times a day in prepared gum extracts (0wt%, 5wt%, and 10wt%) and artificial saliva of pH 7 (Control) for 20 min at 37 °C. Thereafter, remineralization assessment was performed by using Swept Source Optical Coherence Tomography (SS-OCT) and micro-computed tomography (µCT). Surface morphology and elemental analysis were conducted by scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDS). RESULTS: The depths of the demineralized lesions in the GE5 and GE10 groups were significantly lower than those of the Control and the GE0 groups. SEM observations of the enamel surface morphology of the GE5 and GE10 groups indicated remineralization with S-PRG filler-related elements present. CONCLUSION: The GE5 and GE10 S-PRG filler containing gum-base materials showed significantly improved surface remineralization and reduced demineralization of the enamel lesions. EDS analysis suggested that the released ions from the S-PRG filler might be responsible for surface remineralization. CLINICAL SIGNIFICANCE: The S-PRG filler containing gum-base material may have a significant remineralization effect and improve the surface morphology of enamel subsurface lesions.

High-Intensity Interval Training Induces Protein Lactylation in Different Tissues of Mice with Specificity and Time Dependence.

Protein lysine lactylation (Kla) is a novel protein acylation reported in recent years, which plays an important role in the development of several diseases with pathologically elevated lactate levels, such as tumors. The concentration of lactate as a donor is directly related to the Kla level. High-intensity interval training (HIIT) is a workout pattern that has positive effects in many metabolic diseases, but the mechanisms by which HIIT promotes health are not yet clear. Lactate is the main metabolite of HIIT, and it is unknown as to whether high lactate during HIIT can induce changes in Kla levels, as well as whether Kla levels differ in different tissues and how time-dependent Kla levels are. In this study, we observed the specificity and time-dependent effects of a single HIIT on the regulation of Kla in mouse tissues. In addition, we aimed to select tissues with high Kla specificity and obvious time dependence for lactylation quantitative omics and analyze the possible biological targets of HIIT-induced Kla regulation. A single HIIT induces Kla in tissues with high lactate uptake and metabolism, such as iWAT, BAT, soleus muscle and liver proteins, and Kla levels peak at 24 h after HIIT and return to steady state at 72 h. Kla proteins in iWAT may affect pathways related to glycolipid metabolism and are highly associated with de novo synthesis. It is speculated that the changes in energy expenditure, lipolytic effects and metabolic characteristics during the recovery period after HIIT may be related to the regulation of Kla in iWAT.

Efficacy of concurrent chemoradiotherapy with retrograde super selective intra-arterial infusion combined with cetuximab for synchronous multifocal oral squamous cell carcinomas.

BACKGROUND: The incidence of multicentric oral cancer is increasing. However, treatment encounters difficulty if each tumor needs to be treated simultaneously. The objective of this clinical case report is to highlight the effect of concurrent chemoradiotherapy with retrograde superselective intra-arterial infusion combined with systemic administration of cetuximab on synchronous multifocal oral squamous cell carcinomas. CASE PRESENTATION: A 70-year-old man presented to the hospital with multiple tumors and oral pain. Three independent tumors were found in the right dorsal tongue, left edge of the tongue, and left lower lip. Based on the characteristic appearance of the lesions and further evaluation, clinical diagnoses of right tongue cancer "T3", left tongue cancer "T2" and lower left lip cancer "T1", N2cM0 were made. Treatment was initiated with systemic administration of cetuximab, followed by intra-arterial chemoradiotherapy. Treatment results were complete response on all three local lesions, and left neck dissection was performed following the initial treatment. The patient showed no evidence of recurrence during the 4 years follow-up period. CONCLUSIONS: This novel combination treatment seems to be a promising strategy for patients with synchronous multifocal oral squamous cell carcinoma.

A Lightweight AlCrTiV0.5Cux High-Entropy Alloy with Excellent Corrosion Resistance.

Lightweight high-entropy alloys (HEAs) are a new class of low-density, high strength-to-weight ratio metallic structural material. Understanding their corrosion behavior is crucial for designing microstructures for their practical applications. This work investigates the electrochemical corrosion behavior of lightweight HEAs AlCrTiV0.5Cux (x = 0, 0.2, 0.4, 0.6, 0.8, and 1.0) in a 0.6 M NaCl solution. These HEAs were produced by vacuum arc melting. In contrast to 304L stainless steel, all of the alloys exhibited lower current density levels caused by self-corrosion, with AlCrTiV0.5 demonstrating the highest corrosion resistance (0.131 µA/cm2). Corrosion resistance decreased along with the content of copper because copper segregation accelerated local corrosion throughout the alloy.

Time-dependent structural changes and hypermineralisation of artificially demineralised dentine following treatment with silver diammine fluoride and glass ionomer cement.

OBJECTIVES: This study aimed to evaluate the change of mineral content in dentine lesions over time and examine the effectiveness of the combined treatment with silver diammine fluoride (SDF) and glass ionomer cement (GIC). METHODS: Sixty bovine dentine specimens were divided into 4 groups: cont, Fuji, Safo, and Safo+Fuji. The specimens were imaged and measured using microcomputed tomography (microCT) at 7 time points: pre-demineralisation, after demineralisation for two weeks, immediately after treatment, 1 week, 2 weeks, 1 month, and 3 months after treatment. The 3-month group was evaluated with a light microscope, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, and scanning electron microscope (SEM)/energy-dispersive X-ray spectroscopy (EDS). Data were analysed by Dunn's test and Wilcoxon signed rank test with Bonferroni correction for microCT, and Kruskal-Wallis test and two-way analysis of variance for EDS characterisation. RESULTS: MicroCT images showed high mineral density beneath dentine lesions in Safo+Fuji. The mineral density at 600 µm in Safo+Fuji increased significantly over time, while Safo showed an opposite trend (adjusted p<0.005). In Safo+Fuji, EDS revealed significantly high energy of fluorine (p<0.05, at 300 µm) and a tendency towards high energy of calcium (p>0.05). However, Safo+Fuji showed lower energy of silver compared to Safo (p<0.001). ATR-FTIR revealed that phosphate groups had the highest peak at a depth between 300 and 400 µm in Safo+Fuji. CONCLUSIONS: Safo+Fuji was effective in remineralising the deep lesion in dentine after one and three months, and a hypermineralisation zone generated beneath the lesion demonstrated additional benefit in this study. CLINICAL SIGNIFICANCE: This long-term in vitro study showed that SDF+GIC treatment could strengthen the structure of decayed teeth when applied in the treatment of patients with advanced rampant caries.

Development of HPLC-MS/MS assay for quantitation of ensartinib in human plasma and its application to a pharmacokinetics study in Chinese patients.

Ensartinib is a novel anaplastic lymphoma kinase (ALK) inhibitor with potent activity against a broad range of known crizotinib-resistant ALK mutations and is developed to treat patients with non-small-cell lung cancer. This study was the first to develop and validate a rapid and sensitive HPLC-MS/MS method for the determination of ensartinib in human plasma. The plasma samples were extracted using liquid extraction, and chromatographic separation was performed using a Phenomenex, Luna phenyl-hexyl column (50 × 2.0 mm, 5 µm). Electrospray ionization in positive-ion mode and multiple reaction monitoring were used to monitor ion transitions at m/z 561.3 → 257.1 (ensartinib) and 565.2 → 261.2 (internal standard: X-396-d4), respectively. The method yielded excellent linearity in the range of 0.5-500 ng/ml with the lowest quantification of 0.5 ng/ml. Both intra- and inter-run precisions (relative standard deviation %) were less than 15%, with accuracy (relative error %) between ±15%. Extraction recovery, matrix effect, selectivity, and stability were also validated and found to be satisfactory. Finally, the validated method was successfully applied in a phase I clinical study of ensartinib in Chinese subjects with advanced ALK-positive non-small-cell lung cancer.

Fabrication and Characterization of Electrospun Poly(Caprolactone)/Tannic Acid Scaffold as an Antibacterial Wound Dressing.

Antibacterial wound dressings are promising materials to treat infected skin wounds, which greatly affect the wound-healing process. In this study, tannic acid (TA), a natural antibacterial agent, was successfully loaded by electrospinning into poly(caprolactone) (PCL) fibers in a high concentration. It is suggested that the addition of TA was beneficial for producing uniform and continuous PCL nanofibers. Hydrogen bonds existed between the PCL and TA molecules based on the analysis of FTIR spectra and DSC results. The interactions and continuous network improved the mechanical properties of the scaffolds. Meanwhile, increasing the amount of TA also enhanced the hydrophilicity and water absorption capacity of the scaffold, both of which are beneficial for accelerating wound healing. Moreover, a burst release of the TA in the initial stage and a controlled, steady release behavior over time contributed to the highly antibacterial properties of the PCL/TA scaffolds. The fabrication of the composite scaffold supplies a facile, efficient, and controllable approach to address the issue of antibacterial treatment in wound dressing.

Relationship between social network and individual performance of core members from aged care services social organizations: cross-sectional study.

BACKGROUND: The social network of core members can affect the performance of the organization, while there is a lack of research on the relationship between the social network of core members of social organizations and individual performance in the field of aged care services. This study aimed to explore the relationship between social network and individual performance of core members from social organizations engaged in aged care services and explore measures to promote the development of aged care services. METHODS: We used a multi-stage stratified sampling method to conduct a cross-sectional study and collected the required data in six cities in Anhui Province, China. Univariate analysis and binary logistic regression were used to estimate the relationship between social network and individual performance. RESULTS: Our results indicated that core members with higher social network scores were more likely to yield better individual performance, including receiving awards or recognitions related to aged care services (AOR=2.534; 95% CI: 1.397-4.596). Moreover, teams led by the core members were more likely to receive awards or recognitions related to aged care services (AOR=2.930; 95% CI: 1.740-4.933). The core members or the teams led by them were more likely to be reported by the media (AOR=1.748; 95% CI: 1.030-2.966) and participate in the drafting or discussion of local aged care service standards or service specifications (AOR=2.088; 95% CI: 1.093-3.911). In addition, demographic variables such as gender, marital status, and education of core members were significantly related to their performance (P<0.05). CONCLUSIONS: The social network of core members of aged care service social organizations has an impact on their individual performance. To improve the performance of the core members of senior citizens services and organizations, relevant measures should be taken from the government, social organizations and core members to strengthen the social network construction of core members.