Quantifying chemical correlations between fruits and processed fruit products: A non-targeted analysis approach.

Juices and beverages are produced by industry for long-distance distribution and shelf-stability, providing valuable nutrients. However, their nutritional value is often underestimated due to insufficient analytical methods. We have employed non-targeted analysis through a standardized analytical protocol, taking advantage of Data Independent Acquisition (DIA) technique and a novel Chromatographic Retention Behavior (CRB) data deconvolution algorithm. After analyzing 9 fruits and their products, correlations between fruits and their juices are accurately digitalized by similarities of their LC-MS fingerprints. We also specify non-targeted molecules primarily associate with nutrient loss in these analyzed juice products, including nitrogenous nutrients, flavonoids, glycosides, and vitamins. Moreover, we unveiled previously unreported fruit-characteristic metabolites, of which reconstituted-from-concentrate (RFC) juices contain over 40% of the content found in their fresh counterparts. Conclusively, our method establishes a quantitative benchmark for rational selection of RFC juices to substitute natural fruits.

A meta-analysis for the diagnostic accuracy of SelectMDx in prostate cancer.

To overview the diagnostic accuracy of SelectMDx for the detection of clinically significant prostate cancer and to review sources of methodologic variability. Four electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library were searched for eligible studies investigating the diagnostic value of SelectMDx compared with the gold standard. The pooled sensitivity, specificity, and positive and negative predictive values were calculated. Included studies were assessed according to the Standards for Quality Assessment of Diagnostic Accuracy Studies 2 tool. The review identified 14 relevant publications with 2579 patients. All reports constituted phase 1 biomarker studies. Pooled analysis of findings found an area under the receiver operating characteristic analysis curve of 70% [95% CI, 66%-74%], a sensitivity of 81% [95% CI, 69%-89%], and a specificity of 52% [95% CI, 41%-63%]. The positive likelihood ratio was 1.68, and the negative predictive value is 0.37. Factors that may influence variability in test results included the breath collection method, the patient's physiologic condition, the test environment, and the method of analysis. Considerable heterogeneity was observed among the studies owing to the difference in the sample size. SelectMDx appears to have moderate to good diagnostic accuracy in differentiating patients with clinically significant prostate cancer from people at high risk of developing prostate cancer. Higher-quality clinical studies assessing the diagnostic accuracy of SelectMDx for clinically significant cancer are still needed.

Interaction of Cecropin A (1-7) Analogs with DNA Analyzed by Multi-spectroscopic Methods.

Cecropin A (1-7) is a cationic antimicrobial peptide which contain lots of basic amino acids. To understand the effect of basic amino acids on cecropin A (1-7), analogues CA2, CA3 and CA4 which have more arginine or lysine at the N-terminal or C-terminal were designed and synthesized. The interaction of cecropin A (1-7) and its analogs with DNA was studied using ultraviolet-visible spectroscopy, fluorescence spectroscopy and circular dichroism spectroscopy. Multispectral analysis showed that basic amino acids improved the interaction between the analogues and DNA. The interaction between CA4 and DNA is most pronounced. Fluorescence spectrum indicated that Ksv value of CA4 is 1.19 × 105  L mol-1 compared to original peptide cecropin A (1-7) of 3.73 × 104  L mol-1. The results of antimicrobial experiments with cecropin A (1-7) and its analogues showed that basic amino acids enhanced the antimicrobial effect of the analogues. The antimicrobial activity of CA4 against E. coli was eightfold higher than that of cecropin A (1-7). The importance of basic amino acid in peptides is revealed and provides useful information for subsequent studies of antimicrobial peptides.

Several laboratory variables indicate severity and prognosis of COVID-19.

OBJECTIVE: While several laboratory variables have been used to assess COVID-19 disease, to our knowledge, no attempt has previously been made to compare differences across different patient groups. We attempted to evaluate the relationship between laboratory variables and severity of the disease as well as on prognosis. METHOD: We searched BioLINCC database and identified three studies which had separately included outpatients, inpatients, and ICU patients. For this re-analysis, we extracted data on general demography, laboratory variables and outcome. RESULT: In total, 2454 participants (496 outpatients [Study 1], 478 inpatients [Study 2], and 1480 ICU patients [Study 3]) were included in the analysis. We found three laboratory variables (i.e., creatinine, aspartate transferase, and albumin) were not only prognostic factors for outcome of inpatients with COVID-19, but also reflected disease severity as they were significantly different between inpatients and ICU patients. These three laboratory variables are an indication of kidney function, liver function, and nutritional status. CONCLUSION: For patients with COVID-19, in addition to monitoring infectious disease indicators, we need to pay attention to liver function, renal function, and take timely measures to correct them to improve prognosis.

Biomimetic urine flow control can preserve bladder function in patients with indwelling catheterization.

For patients with long-term indwelling catheterization, bladder function will be affected. It is necessary to explore whether biomimetic urine flow control (BUFC) can improve bladder function in patients undergoing indwelling catheterization. A retrospective, data-only, cohort study was carried out. The patients admitted to the intensive care unit, who had retained catheter and been continuously using a urodynamic monitoring system for over 30 days were selected. They were divided into 2 groups based on whether they were using BUFC function. The urodynamic monitoring data of the 2 groups were compared and analyzed. A total of 30 patients were included in the final analysis, including 15 in the BUFC group and 15 in the unobstructed group. The Urinary Volume and maximal urinary flow rate of the unobstructed group showed a continuous downward trend, while the BUFC group remained stable, and there was a statistical difference (P < .05) between the 2 groups since day 20. The bladder ultrasound imaging showed that the bladder volume of the BUFC group did not decrease significantly on the 30th day. BUFC technology, which provided by a urodynamic monitoring system, has potential protective effects of the bladder function after indwelling catheterization.

Rapid and sensitive determination of free fatty acids based on in-source microdroplet-driven derivatization coupled with high-resolution mass spectrometry.

Accurate and sensitive measurements of free fatty acids (FFAs) in biological samples are valuable for diagnosing and prognosing diseases. In this study, an in-source microdroplet derivation strategy combined with high-resolution mass spectrometry was developed to analyze FFAs in lipid extracts of biological samples directly. FFAs were rapidly derivated with 2-picolylamine (PA) in the microdroplet which is derived by electrospray. With the proposed method, twelve typical FFAs were determined reliably with high sensitivity and acceptable linearities (R2 ≥ 0.94). The LODs and LOQs for the twelve FFAs were 9-76 pg mL-1 and 30-253 pg mL-1, respectively. The developed method was applied to analyze the alteration of FFAs in liver and kidney samples of rats induced by perfluorooctane sulfonate (PFOS) exposure. The good results demonstrate that the established analysis technique is dependable and has promising applications in detecting FFAs associated with complex biological samples.

Early diagnosis for pulmonary embolism: A systematic review and meta-analysis.

BACKGROUND: The incidence of acute pulmonary embolism (APE) (especially early diagnosis) has increased annually in recent years, but the diagnosis of APE is a great challenge for every clinician. However, few studies have evaluated multiple diagnostic indicators simultaneously. METHODS: A systematic search was performed using CNKI, Wan fang data, VIP, PubMed and Web of Science for studies on the diagnosis of pulmonary embolism published up to October 31, 2022. Using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), we evaluated the risk of bias in included studies, and used a random-effects meta-analysis to obtain the summary sensitivity and specificity. The data that were extracted and calculated for this study included the first author, year of publication, country, study type, sample size, disease type, gold standard, diagnostic indicators and 4-compartment table data. We strictly followed the Preferred Reporting Items for Systematics reviews and Meta-Analysis (PRISMA) guidelines in this review. RESULTS: This study included 30 articles with a total sample size of 8947 cases, involving 4 detection methods: D-dimer, Geneva rules, Wells rules, and lung imaging. The combined effect size showed that lung imaging had the highest diagnostic value (SEN = 0.95, SPE = 0.89), followed by D-dimer (SEN = 0.92, SPE = 0.60), Geneva rules (SEN = 0.78, SPE = 0.68), and Wells rules (SEN = 0.77, SPE = 0.67). The area of lung imaging was largest under the Summary Receiver Operator Characteristic (SROC) curve (AUC = 0.97), followed by Geneva rules (AUC = 0.80), Wells rules (AUC = 0.79), and D-dimer (AUC = 0.74). CONCLUSION: All 4 detection methods showed good ability to diagnose PE, and lung imaging was the best. Clinical trials are recommended to build an early decision-making model for the diagnosis of pulmonary embolism in order to increase the detection rate and improve prognosis.

Recent progress and clinical applications of advanced biomaterials in cosmetic surgery.

Materials of different allogeneic or xenogeneic or autologous origins are widely used as soft-tissue fillers or structural scaffolds in the field of cosmetic surgery, while complications including prosthesis infection, donor site deformity and filler embolization have always been difficult problems for plastic surgeons. The application of novel biomaterials may bring in hopeful solutions for these problems. Recently, some advanced biomaterials, such as regenerative biomaterials can effectively promote the repair of defective tissues, which have been proven to have good therapeutic as well as cosmetic effects in cosmetic surgery. Therefore, biomaterials with active compounds have drawn significant attention for the tissue regeneration of reconstructive and esthetic treatment. Some of these applications have achieved better clinical outcomes than traditional biological materials. This review summarized recent progress and clinical applications of advanced biomaterials in cosmetic surgery.

Parthenolide Attenuates Sepsis-Induced Acute Kidney Injury in Rats by Reducing Inflammation.

Background: Sepsis is a common complication of severe trauma, burns, infection, or major surgery. This disease-related end-organ dysfunction results from systemic inflammatory response syndrome (SIRS). Acute kidney damage (AKI), also known as acute renal failure, is one of the most frequent and serious sequelae of sepsis. Nuclear transcription factor-κB (NF-κB) regulates the transcription of inflammation-related genes and operates as a mediator in the immune system. While parthenolide (PTL) has been reported to prevent harmful inflammatory reactions, its effects on sepsis-associated AKI are unknown. The current study investigates the effects of PTL in sepsis-associated AKI using cell and cecal ligation and puncture (CLP) models. Methods: Lipopolysaccharide (LPS)-stimulated rat glomerular mesangial cells were treated with 10 µM PTL. Inflammatory mediators, including TNF-α, IL-6, and IL-1ß, in the culture supernatants were measured by ELISA, and NF-κB levels were assessed by qPCR. After the generation of the septic CLP model, rats were intraperitoneally injected with 500 g/kg PTL and were euthanized after 72 h. Serum and kidney samples were analyzed. Results: TNF-α, IL-1ß, and IL-6 levels were elevated after LPS treatment of rat glomerular mesangial cells (p=0.004, p=0.002, and p=0.004, respectively) but were significantly reduced in the PTL treatment group (p ≤ 0.001, p=0.01, and p ≤ 0.001). NF-κB p65 levels were also increased after LPS treatment in this group and were reduced in the PTL treatment group. PTL treatment also reduced kidney damage after CLP induction, as shown by histological analysis and reductions in the levels of BUN, Cre, KIM-1, and NAGL. CLP-induced kidney inflammation together with increased levels of proinflammatory cytokines and inflammatory-related proteins. The elevated levels of renal TNF-α, IL-6, and IL-1ß were downregulated after PTL treatment. The PTL treatment also reduced the CLP-induced activation of NF-κB p65 in the damaged kidneys. Conclusion: PTL reduced inflammation induced by CLP-induced AKI in rat models and LPS-induced damage to glomerular mesangial cells by suppressing NF-κB signaling.

Nanoparticle-Delivered Transforming Growth Factor-ß1 siRNA Induces PD-1 against Gastric Cancer by Transforming the Phenotype of the Tumor Immune Microenvironment.

Immune checkpoint blockade (ICB) is currently considered to be an important therapeutic method, which obtained FDA approval for clinical use in gastric cancer in 2017. As a new mechanism, it was found that the effect of αPDL1 could be improved by blocking the TGF-ß1 signaling pathway, which converts the tumor immune microenvironment from the "immune-excluded phenotype" to the "immune-inflamed phenotype". Based on this phenomenon, this project was designed to prepare TGF-ß1-siRNA-loaded PEG-PCL nanoparticles conjugated to αPDL1 (siTGF-ß1-αPDL1-PEG-PCL) since we have linked similar antibodies to PEG-PCL previously. Therefore, MFC tumor-engrafted mice were established to simulate the biological characteristics of converting the phenotype of the immune microenvironment, and to study the anti-tumor effect and possible molecular mechanism. In this study, αPDL1 antibody conjugates markedly increased the cell uptake of NPs. The produced αPDL1-PEG-PCL NPs efficiently reduced the amounts of TGF-ß1 mRNA in MFC cells, converting the immune microenvironment of MFC tumors engrafted mice from the "immune-excluded phenotype" to the "immune-inflamed phenotype". PDL1-harboring gastric cancer had increased susceptibility to αPDL1. The value of this drug-controlled release system targeting the tumor microenvironment in immune checkpoint therapy of gastric cancer would provide a scientific basis for clinically applying nucleic acid drugs.

Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia: An Overview of Systematic Reviews.

Background: Hematopoietic stem cell transplantation (HSCT) has become the main treatment for acute myeloid leukemia (AML) and has been studied in many systematic reviews (SRs), but strong conclusions have not been drawn yet. Objective: This study aimed to summarize and critically evaluate the methodological and evidence quality of SRs and meta-analysis on this topic. Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched for SRs/meta-analyses regarding HSCT for AML. Two reviewers assessed the quality of SRs/meta-analyses in line with AMSTAR-2 and evaluated the strength of evidence quality with the grading of the evaluation system (GRADE) for concerned outcomes independently. Results: 12 SR/Meta articles were included, and the AMSTAR-2 scale showed that the quality grade of all articles was low or very low. GRADE results showed 29 outcomes, 2 of which were high, 12 were moderate, and 15 were low. Limitations and inconsistency were the most important factors leading to degradation, followed by imprecision and publication bias. Allo-SCT had better OS and DFS benefits than auto-SCT and significantly reduced the relapse in intermediate-risk AML/CR1 patients. Auto-SCT was associated with lower TRM than allo-SCT but generally had higher relapse. The results should be confirmed further for the low or moderate evidence quality. Conclusion: Current SRs show that allo-SCT in the treatment of AML might improve the OS, RFS, and DFS. Auto-SCT has significantly lower TRM but higher RR. Whether bone marrow transplantation is superior to nonmyeloablative chemotherapy remains to be evaluated. Meanwhile, the quality of methodology needs to be further improved. The intensity of evidence was uneven, and the high-quality evidence of outcomes was lacking. Considering the limitations of our overview, more rigorous and scientific studies are needed to fully explore the efficacy of different interventions of HSCT in AML, and clinicians should be more cautious in the treatment.

Value of digital PCR in the early diagnosis of sepsis: A systematic review and meta-analysis.

BACKGROUND: We systematically assessed whether a digital polymerase chain reaction (PCR) could detect pathogenic microorganisms in patients with sepsis early and accurately. METHODS: We searched the Cochrane Library, MEDLINE, Embase, CNKI, CBM, and Wanfang Data databases for eligible studies to compare the detection of pathogenic microorganisms in blood samples by digital PCR with the gold standard. The Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate bias risk, and a random-effects meta-analysis approach was used for sensitivity and specificity calculations. RESULTS: Among the eight articles, there were eight identified studies with a total of 1278 subjects. The pooled sensitivity of digital PCR was 94% (95% confidence interval [CI], 85%-98%), the specificity was 87% (95% CI, 76%-94%), the positive likelihood ratio was 7.3 (95% CI, 3.8-14.2), the negative likelihood ratio was 0.07 (95% CI, 0.03-0.17), the positive predictive value was 84.7%, the negative predictive value was 89.2%, the diagnostic odds ratio was 105 (95% CI, 37-303), and the area under the receiver operating characteristic curve was 0.97 (95% CI, 0.95-1.00). Digital PCR can shorten the detection time of pathogenic microorganisms in patients with sepsis. CONCLUSIONS: Digital PCR can detect pathogenic microorganisms in patients with sepsis earlier than blood culture. Therefore, digital PCR can be used as a potential strategy for the detection of pathogenic microorganisms in patients with sepsis.

Early Warning of Enterprise Financial Risk Based on Decision Tree Algorithm.

To improve enterprise financial early warning, we propose an algorithm based on a decision tree. According to the shortcomings and defects of the classical algorithm and the traditional decision tree algorithm, in the ordinary decision tree improved algorithm based on PCA, there is a problem that the representativeness of the data after dimensionality reduction processing are not high, resulting in the fact that the accuracy of the algorithm can be improved slightly after multiple data runs. Based on the classical algorithm, attribute eigenvalues before classification are extracted twice, and the amount of data to be classified is calculated. That is, the most important attributes of the original data are selected. After the subtree is established, the dimension reduction and merging selection of the data are performed, and the improved algorithm is verified by using three data sets in the UCI database. The results show that the average accuracy in the three datasets is 94.6%, which is improved by 1.6% and 0.6% for the traditional classical algorithm and the ordinary PCA decision tree optimization algorithm, respectively. PCA-based decision tree algorithms can improve the accuracy of the results to some extent, which is of practical importance. In the future, a classic algorithm improved for secondary modeling will be used to obtain a more efficient decision tree model. The decision tree algorithm has been proven to recognize an early warning of an enterprise's financial risks, which enhances the effectiveness of an enterprise's early financial warning.

Three-Dimensional Printing of Large-Scale, High-Resolution Bioceramics with Micronano Inner Porosity and Customized Surface Characterization Design for Bone Regeneration.

Three-dimensional printing technologies have opened up new possibilities for manufacturing bioceramics with complex shapes in a completely digital fabrication process. Some bioceramics have demonstrated elaborate design and high resolution in their small parts through digital light projection (DLP) printing. However, it is still a challenge to prepare large-scale, high-precision ceramics that can effectively regulate the bioactivity of materials. In this study, we fabricated a large-scale hydroxyapatite porous bioceramic (length >150 mm) using DLP. This bioceramic had highly micronanoporous surface structures (printing resolution <65 µm), which could be controlled by adjusting the solid content and sintering process. Both in vitro and in vivo results indicated that the designed bioceramic had promising bone regeneration ability. This study provides significant evidence for exploring the effects of microenvironments on bone tissue regeneration. These results indicated that DLP technology has the potential to produce large-scale bone tissue engineering scaffolds with accurate porosity.

Characteristics of Depression Clinical Trials Registered on ClinicalTrials.gov.

Background: Mental disorders are among the leading causes of the global health-related burden, and depression is one of the most disabling mental disorders. The emergence of the COVID-19 pandemic has created an environment where many determinants of mental health are exacerbated. Many studies have been registered and conducted over the past 16 years, but how to choose the proper design for depression clinical trials remains the main concern. This study aimed to characterize the current status of global depression clinical trials registered on ClinicalTrials.gov. Methods: We examined all the trials registered on ClinicalTrials.gov from 2007 to 2021. Results: Overall, 7623 depression clinical trials were identified for analysis. Of those trials, 6402 (83.98%) were intervention trials and 1212 (15.90%) were observational trials. The majority of intervention types were behavioral (35.2%) and drug (28.55%), with very few procedures, dietary supplements, and diagnostic test studies. In addition, 55.53% of trials enrolled <100 participants. The proportions of trials registered in North America were higher than on other continents. Furthermore, the trials that involved only females (12.6%) were more than only males (0.87%) from 2019 to 2021. Conclusion: Depression clinical trials registered on ClinicalTrials.gov were dominated by small sample size trials, and there is a lack of trials related to COVID-19. The choice of study design is crucial, and properly designed trials can help improve study efficiency and reduce the likelihood of study failure. Given the increased number of RCT trials, the trial quality is gradually improving over the years. In addition, depression trials concentrating on children and older adults need more scientific attention. Further studies related to COVID-19 are needed, given the great damage that causes to people's physical and mental health.

lncRNA OGFRP1 promotes tumor progression by activating the AKT/mTOR pathway in human gastric cancer.

As biomolecules of great clinical value, lncRNAs play a crucial role as regulators in the processes of tumor origin, metastasis, and recurrence. Thus, lncRNAs are urgently needed for research in gastric cancer. We elucidated the specific function of OGFRP1, both in vitro and in vivo. OGFRP1 was expressed at abnormally high levels in gastric cancer samples (n = 408) compared to normal samples (n = 211). Similar results were obtained in 30 clinical case samples. Interference of OGFRP1 markedly blocked cell proliferation and migration, and it induced cell cycle arrest and the apoptosis of gastric cancer cells in vitro. Phosphorylation of AKT was inhibited in cells transfected with OGFRP1 siRNA, as compared to their control cells. The in vivo results further confirmed the antitumor effects of OGFRP1 knockdown on gastric cancer. Decreases in tumor volume (104.23±62.27 mm3) and weight (0.1006±0.0488 g) in nude mice were observed during the OGFRP1 interference, as compared with the control group (418.96±211.96 mm3 and 0.2741±0.0769 g). OGFRP1 promotes tumor progression through activating the AKT/mTOR pathway. Our findings provide a new potential target for the clinical treatment of human gastric cancer.

Tumor Necrosis Factor Alpha Gene Polymorphisms Increase Susceptibility to Adenovirus Infection in Children and Are Correlated with Severity of Adenovirus-Associated Pneumonia.

Objective: To study the relationships between single nucleotide polymorphisms (SNPs) in the intron of the tumor necrosis factor α (TNFα) gene and the susceptibility and severity of disease associated with adenovirus infection in children. Methods: Four polymorphic loci of the TNFα gene (rs3093661, rs1800610, rs3093662, and rs3093664) were characterized allelically and genotypically in 320 children with adenovirus-associated pneumonia (AP) and compared with 320 healthy controls. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the plasma TNFα protein levels in all subjects. Results: The TNFα gene rs3093661 locus A allele, the rs1800610 locus A allele, the rs3093662 locus G allele, and the rs3093664 locus G allele were identified as susceptibility alleles for development of AP, and they were also positively correlated with the severity of AP. In children who had the GGAA haplotype, AP susceptibility was significantly reduced (0.28-fold) (95% confidence interval, CI: 0.20-0.40, p < 0.001). Conversely, among the subjects with the AGGG haplotype, their AP susceptibility risk was significantly increased (2.76-fold) (95% CI: 1.77-4.29, p < 0.001); and in the subjects with the AP GGGG haplotype their AP susceptibility risk was significantly increased (2.49-fold) (95% CI: 1.67-3.72, p < 0.001). The TNFα rs3093661, rs1800610, rs3093662, and rs3093664 SNPs were significantly correlated with plasma TNFα levels (p < 0.05). Conclusion: The TNFα gene rs3093661, rs1800610, rs3093662, and rs3093664 loci are associated with AP susceptibility and severity. This relationship might be due to the effect on TNFα levels found in the plasma. Clinical Trial Registration number: LL20190723.

Low-dose apatinib and tegafur-gimeracil-oteracil as palliative treatment in recurrent cervical cancer patients with poor performance status: A case series.

WHAT IS KNOWN AND OBJECTIVE: A large proportion of recurrent cervical cancer (RCC) patients present with poor performance status (PS) after comprehensive treatments, which usually prevents them from opting for clinical trials. We retrospectively analysed the effect and safety of low-dose apatinib and tegafur-gimeracil-oteracil (TGO) in the treatment of these patients. CASE SUMMARY: Six patients treated with low-dose apatinib and TGO showed a disease control rate of 83.3% and grade 1-2 adverse events (AEs). WHAT IS NEW AND CONCLUSION: This case series indicates that low-dose apatinib and TGO could be considered as palliative therapy for RCC patients with poor PS.

Tfh cell subset biomarkers and inflammatory markers are associated with frailty status and frailty subtypes in the community-dwelling older population: a cross-sectional study.

We conducted a cross-sectional study investigating community-dwelling older population to determine association between immunoscenescence marker, inflammatory cytokines and frailty. Frailty status was classified with 33-item modified frailty index and latent class analysis was applied to explore the latent classes (subtypes) of frailty. In multivariable analysis, higher Tfh2 cells were associated with a higher risk of frailty [1.13(1.03-1.25)] in females, but a lower risk of cognitive and functional frail [0.92(0.86-0.99)] and physiological frail [0.92(0.87-0.98)]. Additionally, a greater risk of multi-frail and physiological frail correlated with low Tfh1 [0.77(0.60-0.99); 0.87(0.79-0.96)] and Tfh17 cells [0.79(0.65-0.96); 0.86(0.78-0.94)], respectively. Higher B cells were associated with decreased frailty/pre-frailty both in females [0.89(0.81-0.98)] and males [0.82(0.71-0.96)], but did not correlate with frailty subtypes. Regarding inflammatory markers, participants in the TGF-ß 2nd quartile showed a decreased risk of pre-frailty/frailty in females [0.39(0.17-0.89)] and psychological frail [0.37(0.16-0.88)], compared with those in the top tertile. Moreover, we found participants in the 2nd tertile for IL-12 levels showed a decreased risk of physiological frail [0.40 (0.17-0.97)]. Our study highlights the importance of Tfh cell subsets and inflammatory markers in frailty in a sex-specific manner, particularly in terms of frailty subtype.

Direct 3-D printing of Ti-6Al-4V/HA composite porous scaffolds for customized mechanical properties and biological functions.

Customized scaffold plays an important role in bone tissue regeneration. Precise control of the mechanical properties and biological functions of scaffolds still remains a challenge. In this study, metal and ceramic biomaterials are composited by direct 3-D printing. Hydroxyapatite (HA) powders with diameter of about 25 µm and Ti-6Al-4V powders with diameter of 15-53 µm were mixed and modulated for preparing 3-D printing inks formulation. Three different proportions of 8, 10, and 25 wt.% HA specimens were printed with same porosity of 72.1%. The green bodies of the printed porous scaffolds were sintered at 1,150°C in the atmosphere of argon furnace and conventional muffle furnace. The porosities of the final 3-D-printed specimens were 64.3 ± 0.8% after linear shrinkage of 6.5 ± 0.8%. The maximum compressive strength of the 3-D-printed scaffolds can be flexibly customized in a wide range. The maximum compressive strength of these scaffolds in this study ranged from 3.07 to 60.4 MPa, depending on their different preparation process. The phase composition analysis and microstructure characterization indicated that the Ti-6Al-4V and HA were uniformly composited in the scaffolds. The cytocompatibility and osteogenic properties were evaluated in vitro with rabbit bone marrow stromal cells (rBMSCs). Differentiation and proliferation of rBMSCs indicated good biocompatibility of the 3-D-printed scaffolds. The proposed 3-D printing of Ti-6Al-4V/HA composite porous scaffolds with tunable mechanical and biological properties in this study is a promising candidate for bone tissue engineering.