Multilocus Distance-Regulated Sensor Array for Recognition of Polyphenols via Machine Learning and Indicator Displacement Assay.

Developing new strategies to construct sensor arrays that can effectively distinguish multiple natural components with similar structures in mixtures is an exceptionally challenging task. Here, we propose a new multilocus distance-modulated indicator displacement assay (IDA) strategy for constructing a sensor array, incorporating machine learning optimization to identify polyphenols. An 8-element array, comprising two fluorophores and their six dynamic covalent complexes (C1-C6) formed by pairing two fluorophores with three distinct distance-regulated quenchers, has been constructed. Polyphenols with diverse spatial arrangements and combinatorial forms compete with the fluorophores by forming pseudocycles with quenchers within the complexes, leading to varying degrees of fluorescence recovery. The array accurately and effectively distinguished four tea polyphenols and 16 tea varieties, thereby demonstrating the broad applicability of the multilocus distance-modulated IDA array in detecting polyhydroxy foods and natural medicines.

Evaluating the efficacy of combined flap coverage, antibiotic-loaded bone cement and negative pressure irrigation in traumatic osteomyelitis management.

Traumatic osteomyelitis with accompanying soft tissue defects presents a significant therapeutic challenge. This prospective, randomised controlled trial aims to evaluate the efficacy of antibiotic-impregnated bone cement, flap coverage and negative pressure sealed irrigation in the management of traumatic osteomyelitis complicated by soft tissue defects. A total of 46 patients with clinically diagnosed traumatic osteomyelitis and soft tissue defects were randomised into a control group (n = 23) and an observation group (n = 23). The control group underwent standard flap coverage and negative-pressure lavage, while the observation group received an additional treatment with antibiotic-loaded bone cement. Efficacy was measured based on clinical criteria, surgical metrics and morphometric assessment of bone and soft tissue defects. Statistical analyses were performed using SPSS version 27.0. The observation group, treated with an integrated approach of flap coverage, negative pressure wound therapy (NPWT) and antibiotic-impregnated bone cement, demonstrated significantly higher overall treatment efficacy (91.3%) compared to the control group, which received only flap coverage and NPWT (65.2%) (p < 0.01). This enhanced efficacy was evidenced through various outcomes: the observation group experienced reduced surgical times, shorter hospital stays, fewer dressing changes and accelerated wound healing, all statistically significant (p < 0.001). Additionally, a quantitative analysis at 6-month post-treatment revealed that the observation group showed more substantial reductions in both bone and soft tissue defect sizes compared to the control group (p < 0.001). The multi-modal treatment strategy, combining skin flap coverage, antibiotic bone cement and negative-pressure irrigation, showed marked efficacy in treating traumatic osteomyelitis and associated soft tissue defects. This approach accelerated postoperative recovery and lowered costs.

Novel 6-amino-1,3,5-triazine derivatives as potent BTK inhibitors: structure-activity relationship (SAR) analysis and preliminary mechanism investigation.

Bruton's tyrosine kinase (BTK) is a promising drug target for the treatment of B-cell related malignancies. Irreversible inhibition of BTK by a covalent inhibitor has been proved to be a clinically effective therapy. However, most irreversible BTK inhibitors also inhibit other kinases including JAK3 and EGFR, leading to some adverse events. Herein, we reported the structure-based design and optimization of a series of irreversible BTK inhibitors bearing the 6-amino-1,3,5-triazine scaffold. Most of the synthesized compounds demonstrated considerable BTK inhibition and improved anti-proliferative activity against Raji and Ramos cells. Among them, compound C11 exhibited potent BTK inhibition (BTK IC50 = 17.0 nM) and a desirable selectivity profile especially over EGFR. Moreover, C11 effectively blocked activation of BTK and downstream signaling, arrested the cell cycle in G0/G1 phase and induced apoptosis in Raji cells. Its irreversible binding mode was further investigated by both molecular modeling and a washout experiment. Collectively, C11 is a novel selective irreversible BTK inhibitor worthy of further in-depth research.

Structural optimization of tetrahydroisoquinoline-hydroxamate hybrids as potent dual ERα degraders and HDAC inhibitors.

Both estrogen receptor α (ERα) and histone deacetylases (HDACs) are valid therapeutic targets for anticancer drug development. Combination therapies using diverse ERα antagonists or degraders and HDAC inhibitors have been proven effective in endocrine-resistant ER + breast cancers based on the crosstalk between ERα and HDAC pathway. In this study, we reported the optimization of a series of methoxyphenyl- or pyridinyl- substituted tetrahydroisoquinoline-hydroxamates, which were optimized from 31, a dual ERα degrader/HDAC inhibitor previously reported by our group. Most of the synthesized compounds displayed potent ERα degradation efficacy and antiproliferative activity. Among them, A04 demonstrated the best anti-proliferation activity (MCF-7 IC50 = 1.96 µM) and HDAC6 inhibitory activity (HDAC6 IC50 = 25.96 nM), which is slightly more potent than the lead compound 31 (MCF-7 IC50 = 4.38 µM, HDAC6 IC50 = 63.03 nM). In addition, compound A04 exerted ERα-independent HDAC6-inhibiting effect without agonistic activity in endometrial cells. These results demonstrated that A04 is a novel and promising dual ERα degrader/HDAC inhibitor worthy of further development.

Two new alkaloids from a strain of endophytic fungus Aspergillus sp.

19-Hydroxybrevianamide M (1) and 6 R-methoxybrevianamide V (2), two new alkaloids, were isolated from an extract of the endophytic fungus Aspergillus sp. JNU18HC0517J, together with six known analogues (3- 8). Their structures were elucidated by extensive spectroscopic analyses, NMR calculations, and ECD calculations. 6 R-methoxybrevianamide V (2) was the first L-proline indole DKP alkaloid with substitution at C-6 on the proline ring. Furthermore, the cytotoxities and antimicrobial activities of these isolated compounds were also evaluated. Compound 8 exhibited moderate antibacterial activity against Staphylococcus aureus 209 P with a minimal inhibitory concentration (MIC) value of 16 µg/ml.[Figure: see text].

Machine Learning-Assisted Pattern Recognition of Amyloid Beta Aggregates with Fluorescent Conjugated Polymers and Graphite Oxide Electrostatic Complexes.

Five fluorescent positively charged poly(para-aryleneethynylene) (P1-P5) were designed to construct electrostatic complexes C1-C5 with negatively charged graphene oxide (GO). The fluorescence of conjugated polymers was quenched by the quencher GO. Three electrostatic complexes were enough to distinguish between 12 proteins with 100% accuracy. Furthermore, using these sensor arrays, we could identify the levels of Aß40 and Aß42 aggregates (monomers, oligomers, and fibrils) via employing machine learning algorithms, making it an attractive strategy for early diagnosis of Alzheimer's disease.

Comparative efficacy of vasoactive medications in patients with septic shock: a network meta-analysis of randomized controlled trials.

BACKGROUND: Catecholamines, especially norepinephrine, are the most frequently used vasopressors for treating patients with septic shock. During the recent decades, terlipressin, vasopressin V1A agonist, and even Ca2+ sensitizer were increasingly used by physicians. The aim of this study is to compare the efficacy of such different kinds of vasoactive medications on mortality among patients with septic shock. METHODS: Relevant randomized controlled trials were identified by searching PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials updated to February 22, 2018. A network meta-analysis was performed to evaluate the effect of different types of vasoactive medications. The primary outcome was 28-day mortality. Intensive care unit (ICU) mortality, hospital and ICU length of stay (LOS), and adverse events were also assessed. RESULTS: A total of 43 trials with 5767 patients assessing 17 treatment modalities were included. Treatments ranking based on surface under the cumulative ranking curve values from largest to smallest were NE/DB 85.9%, TP 75.1%, NE/EP 74.6%, PI 74.1%, EP 72.5%, VP 66.1%, NE 59.8%, PE 53.0%, DA 42.1%, DX 38.2%, SP 27.0%, PA 24.3%, EX 22.8%, LE 21.5%, and DB 13.3% for 28-day mortality. Treatments ranking for ICU mortality were TP/NE 86.4%, TP 80.3%, TP/DB/NE 65.7%, VP/NE 62.8%, NE 57.4%, VP 56.5%, PE 48.4%, DA 33.0%, PA 27.5%, LE 22.1%, and DB 9.9%. The incidence of myocardial infarction was reported with NE/EP 3.33% (n = 1 of 30), followed by EP 3.11% (n = 5 of 161), and then VP 3.10% (n = 19 of 613), NE 3.03% (n = 43 of 1417), DA 2.21% (n = 19 of 858), NE/DB 2.01% (n = 4 of 199), LE 1.16% (n = 3 of 258), and PA 0.39% (n = 1 of 257). The incidence of arrhythmia was reported with DA 26.01% (n = 258 of 992), followed by EP 22.98% (n = 37 of 161), and then NE/DB 20.60% (n = 41 of 199), NE/EP 20.0% (n = 6 of 30), NE 8.33% (n = 127 of 1525), LE 5.81% (n = 15 of 258), PA 2.33% (n = 6 of 257), and VP 1.67% (n = 10 of 600). CONCLUSIONS: The use of norepinephrine plus dobutamine was associated with lower 28-day mortality for septic shock, especially among patients with lower cardiac output.

Lactate dehydrogenase is associated with 28-day mortality in patients with sepsis: a retrospective observational study.

BACKGROUND: Sepsis is a major health care problem, which affects millions of people around the world. Glucose metabolic reprogramming of immune cells plays a crucial role during advancement of sepsis. However, the association between glucose metabolic reprogramming and mortality in patients with sepsis is unclear. Lactate dehydrogenase (LDH) catalyzes the last step of glycolysis. Investigating the relationship between LDH and mortality is important to understand the effect of metabolic reprogramming on prognosis of patients with sepsis. METHODS: A total of 192 patients with sepsis were included in our study. Data on characteristics of patients, biochemical variables, and inflammatory mediator were collected. Association between the level of serum LDH and 28-day mortality was also analyzed. The correlations between serum LDH, interleukin-1ß, creatinine, PaO2/FiO2, and lactate were also observed. The association between LDH and the risk of death was further analyzed. Moreover, receiver operating characteristic curve was depicted to compare the accuracy in prediction of LDH and other variables. RESULTS: There were statistic difference in 28-day mortality between elevated LDH group and normal LDH group (P = 0.021). Level of serum LDH was an independent risk factor for death of patients with sepsis (hazard ratio 1.005, 95% confidence interval 1.002-1.007, P = 0.001). There were significant correlations between LDH, interleukin-1ß (r = 0.514, P = 0.000), creatinine (r = 0.368, P = 0.000), PaO2/FiO2 (r = -0.304, P = 0.000), and lactate (r = 0.560, P = 0.000). The receiver operating characteristic curves showed that the area under the LDH curve for prediction for mortality was 0.783. CONCLUSIONS: Serum LDH is probably associated with 28-day mortality in patients with sepsis.

Structure-guided design and synthesis of isoflavone analogs of GW4064 with potent lipid accumulation inhibitory activities.

Our group has previously reported a series of isoflavone derivatives with antidyslipidemic activity. With this background, a series of isoflavone analogs of GW4064 were designed, synthesized and evaluated the lipid-lowering activity of analogs. As a result, most of compounds significantly reduced the lipid accumulation in 3T3-L1 adipocytes and four of them (10a, 11, 15c and 15d) showed stronger inhibitory than GW4064. The most potent compound 15d exhibited promising agonistic activity for FXR in a cell-based luciferase reporter assay. Meanwhile, 15d up-regulated FXR, SHP and BSEP gene expression and down-regulated the mRNA expression of lipogenesis gene SREBP-1c. Besides, an improved safety profile of 15d was also observed in a HepG2 cytotoxicity assay compared with GW4064. The obtained biological results were further confirmed by a molecular docking study showing that 15d fitted well in the binding pocket of FXR and interacted with some key residues simultaneously.

Design, synthesis, biological evaluation and molecular docking studies of novel 3-aryl-4-anilino-2H-chromen-2-one derivatives targeting ERα as anti-breast cancer agents.

The estrogen receptor (ER) has played an important role in breast cancer development and progression and is a central target for anticancer drug discovery. In order to develop novel selective ERα modulators (SERMs), we designed and synthesized 18 novel 3-aryl-4-anilino-2H-chromen-2-one derivatives based on previously reported lead compounds. The biological results indicated that most of the compounds presented potent ERα binding affinity and possessed better anti-proliferative activities against MCF-7 and Ishikawa cell lines than the positive control tamoxifen. The piperidyl substituted compounds such as 16d and 18d demonstrated strong ERα binding affinities and excellent anti-proliferative activities respectively. Compound 18d displayed the most potent ERα binding affinity with RBA value of 2.83%, while 16d exhibited the best anti-proliferative activity against MCF-7 cells with IC50 value of 4.52±2.47µM. Further molecular docking studies were also carried out to investigate binding pattern of the newly synthesized compounds with ERα. All these results together with the structure-activity relationships (SARs) indicated that these 3-aryl-4-anilino-2H-chromen-2-one derivatives with basic side chain could serve as promising leads for further optimization as novel SERMs.

The effect of early goal-directed therapy on mortality in patients with severe sepsis and septic shock: a meta-analysis.

BACKGROUND: The Surviving Sepsis Campaign has recommended early goal-directed therapy (EGDT) as an essential strategy to decrease mortality among patients with severe sepsis and septic shock. However, three latest multicenter trials failed to show its benefit in the patients with severe sepsis and septic shock. This article was to evaluate the effect of EGDT on the mortality of patients with severe sepsis and septic shock. METHODS: Relevant studies from PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were identified from January 1, 2001 to June 13, 2015. With both randomized controlled trials (RCTs) and non-RCTs selected, a meta-analysis on the effects of EGDT on all identified trials was performed. The primary outcome was the inhospital mortality. In subgroup, RCTs and non-RCTs were analyzed, respectively. RESULTS: A total of five RCTs and 10 non-RCTs involving 3285 patients in EGDT group and 3233 patients in the control group were identified. Pooled analyses of all studies showed significant difference in the inhospital mortality between the EGDT group and the control group (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.74-0.94; P = 0.003) with substantial heterogeneity (χ2 = 24.93, P = 0.04, I(2) = 44%). In subgroup analysis, there were no significant difference in inhospital mortality between the EGDT group and the control group (RR, 0.95; 95% CI, 0.83-1.10; P = 0.51) with no significant difference in heterogeneity (χ2 = 6.62, P = 0.16, I(2) = 40%) in RCTs. In non-RCTs, EGDT significantly reduced inhospital mortality (RR, 0.75; 95% CI, 0.65-0.88; P = 0.0003) with no significant difference in heterogeneity (χ2 = 11.96, P = 0.22, I(2) = 25%). CONCLUSIONS: This meta-analysis suggests that EGDT can significantly reduce the mortality among patients with severe sepsis and septic shock.

Prevalence and factors associated with occupational burnout among HIV/AIDS healthcare workers in China: a cross-sectional study.

BACKGROUND: Burnout is a psychosomatic syndrome characterized by three dimensions (emotional exhaustion [EE], feelings of depersonalization [DP], and reduced personal accomplishment [PA]). We determined the prevalence of burnout and mental health status between HIV/AIDS healthcare workers and other healthcare workers, and determined the factors associated with burnout of HIV/AIDS healthcare workers. METHODS: All participants were asked to complete a self-administered questionnaire. The participants were recruited from the departments of infectious diseases in four hospitals which treated HIV/AIDS. The questionnaire included demographics, the Maslach Burnout Inventory-General Survey (MBI-GS), the Symptom Checklist 90 (SCL-90), the Eysenck Personality Questionnaire (EPQ), and the Trait Coping Style Questionnaire (TCSQ). RESULTS: A total of 512 questionnaires were distributed; 501 questionnaires were completed and collected (the response rate was 97.9 %). After eliminating nine invalid questionnaires (1.80 %), 264 physicians and nurses caring for HIV/AIDS and 228 physicians and nurses caring for other infectious diseases provided valid responses (98.2 %). The HIV/AIDS healthcare workers' scores on the emotional exhaustion (F = 6.350, p = 0.012) and depersonalization dimensions (F = 8.533, p = 0.004) were significantly higher than other healthcare workers. The HIV/AIDS healthcare workers had higher total scores and positive items on the Symptom Checklist 90 (SCL-90) compared with other healthcare workers. Low job satisfaction, serious somatization, interpersonal sensitivity, poor quality of sleep, high psychoticism scores, and use of negative coping styles were frequently associated with burnout. CONCLUSIONS: Burnout was shown to be highly prevalent in HIV/AIDS healthcare workers, 76.9 % of whom met the accepted criteria for burnout. In addition, compared with other healthcare workers, HIV/AIDS healthcare workers experienced lower levels of psychological health. Interventions should be targeted at reducing the occurrence of burnout and alleviating psychological pressure amongst HIV/AIDS healthcare workers.

[Effect of qi benefiting stasis removing method on systemic inflammatory response and coagulation function in MODS patients].

OBJECTIVE: To observe the effect of qi benefiting stasis removing method (QBSRM) on systemic inflammatory response and coagulation function in multiple organ dysfunction syndrome (MODS) patients. METHODS: Totally 40 MODS patients who were admitted to Affiliated Hospital of Nanjing University of Traditional Chinese Medicine between May 2010 to December 2011 were randomly assigned to two groups, the experimental group (21 cases) and the control group (19 cases). Patients in the control group were treated with routine Western therapy, while those in the experimental group additionally took decoction for benefiting qi removing stasis. Inflammatory factors (including interleukin-1, interleukin-6, tumor necrosis factor-alpha) and coagulation parameters [including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and D-dimer (DD)] were observed before treatment, and 3, 7, and 14 days after treatment in the two groups. RESULTS: At day 7 after treatment,levels of interleukin-1, interleukin-6, and PT were significantly lower in the experimental group than in the control group (P < 0.05). At day 14 after treatment, tumor necrosis factor-x and DD were significantly lower in the experimental group than in the control group (P < 0. 05). There was no statistical difference in APTT or FIB at day 3, 7 and 14 after treatment (P > 0.05). CONCLUSION: QBSRM could relieve systemic inflammatory response and improve coagulation functions.

Trained immunity: A link between risk factors and cardiovascular disease.

Cardiovascular diseases are significant contributors to human mortality, closely associated with inflammation. With the changing living conditions and the extension of human lifespan, greater attention has been directed towards understanding the impact of early, long-term events on the development of cardiovascular events. Lifestyle factors such as stress, unhealthy diet and physical inactivity can increase the risk of cardiovascular diseases. Interestingly, even if the risk factors are addressed later, their influence may persist. Recently, the concept of trained innate immunity (TRIM), defined as sustained alterations in the function of innate immunocyte that promote a more robust response to downstream stimuli, has been proposed to be involved in cardiovascular diseases. It is hypothesized that TRIM may serve as a mediator bridging the impacts of aforementioned risk factors. This review aims to elucidate the role of TRIM in cardiovascular diseases and highlight its significance in uncovering new mechanisms and therapeutic targets.

Efficacy of Xuebijing injection for the treatment of acute lung injury: A meta-analysis of randomized controlled trials.

Background: Management guidelines for acute lung injury (ALI) are extremely limited. Xuebijing, a traditional Chinese medicine, exerts therapeutic effects in patients with ALI; however, supportive evidence is currently insufficient. Material and methods: A systematic literature search of seven electronic databases for randomised controlled trials assessing the efficacy of Xuebijing injections in patients with ALI, published from inception to March 31, 2024, was performed. The Risk of Bias assessment tool recommended by The Cochrane Collaboration was used for quality evaluation. Review Manager version 5.3 (R Foundation for Statistical Computing, Vienna, Austria) was used for analysis. Dichotomous variables are expressed as relative risk (RR) and continuous variables as standardised mean difference (SMD). Heterogeneity was assessed using the I 2 statistic and a funnel plot was used to visually assess publication bias. Results: Sixteen studies comprising 1327 patients were included. Xuebijing injection improved oxygenation index (SMD 1.08 [95 % confidence interval (CI) 0.79-1.38]), reduced the incidence of acute respiratory distress syndrome (RR 0.56 [95 % CI 0.42-0.74) and all-cause mortality (RR 0.48 [95 % CI 0.34-0.67]), and decreased serum tumor necrosis factor-alpha (SMD -1.33 [95 % CI -1.50 to -1.17]) and interleukin-6 levels (SMD -1.35 [95 % CI -1.52 to -1.17]). The funnel plot indicated no publication bias. Conclusion: Xuebijing injection may be an effective treatment for ALI. However, this needs to be further confirmed in well-designed, large-sample, randomised controlled trials.

Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway.

OBJECTIVE: To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments. METHODS: A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed. RESULTS: FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05). CONCLUSION: FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

Current and Novel Therapeutics for Articular Cartilage Repair and Regeneration.

Articular cartilage repair is a sophisticated process that has is being recently investigated. There are several different approaches that are currently reported to promote cartilage repair, like cell-based therapies, biologics, and physical therapy. Cell-based therapies involve the using stem cells or chondrocytes, which make up cartilage, to promote the growth of new cartilage. Biologics, like growth factors, are also being applied to enhance cartilage repair. Physical therapy, like exercise and weight-bearing activities, can also be used to promote cartilage repair by inducing new cartilage growth and improving joint function. Additionally, surgical options like osteochondral autograft, autologous chondrocyte implantation, microfracture, and others are also reported for cartilage regeneration. In the current literature review, we aim to provide an up-to-date discussion about these approaches and discuss the current research status.

Biomimetic inducer enabled dual ferroptosis of tumor and M2-type macrophages for enhanced tumor immunotherapy.

Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment which promotes the formation of the immunosuppressive tumor microenvironment (ITME) through multiple mechanisms, severely counteracting the therapeutic efficacy of immunotherapy. In this study, a novel biomimetic ferroptosis inducer (D@FMN-M) capable of ITME regulation for enhanced cancer ferroptosis immunotherapy is reported. Upon tumor accumulation of D@FMN-M, the intratumoral mild acidity triggers the biodegradation of Fe-enriched nanocarriers and the concurrent co-releases of dihydroartemisinin (DHA) and Fe3+. The released Fe3+ is reduced to Fe2+ by consuming intratumoral glutathione (GSH), which promotes abundant free radical generation via triggering Fenton and Fe2+-DHA reactions, thus inducing ferroptosis of both cancer cells and M2-type TAMs. Resultantly, the anticancer immune response is strongly activated by the massive tumor-associated antigens released by ferroptositic cancer cells. Also importantly, the ferroptosis-sensitive M2-type TAMs will be either damaged or gradually domesticated to ferroptosis-resistant M1 TAMs under the ferroptosis stress, favoring the normalization of ITME and finally amplifying cancer ferroptosis immunotherapeutic efficacy. This work provides a novel strategy for ferroptosis immunotherapy of solid tumors featuring TAMs infiltration and immunosuppression by inducing dual ferroptosis of tumor cells and M2-type TAMs.

Recent Advances and Perspective of Nanotechnology-Based Implants for Orthopedic Applications.

Bioimplant engineering strives to provide biological replacements for regenerating, retaining, or modifying injured tissues and/or organ function. Modern advanced material technology breakthroughs have aided in diversifying ingredients used in orthopaedic implant applications. As such, nanoparticles may mimic the surface features of real tissues, particularly in terms of wettability, topography, chemistry, and energy. Additionally, the new features of nanoparticles support their usage in enhancing the development of various tissues. The current study establishes the groundwork for nanotechnology-driven biomaterials by elucidating key design issues that affect the success or failure of an orthopaedic implant, its antibacterial/antimicrobial activity, response to cell attachment propagation, and differentiation. The possible use of nanoparticles (in the form of nanosized surface or a usable nanocoating applied to the implant's surface) can solve a number of problems (i.e., bacterial adhesion and corrosion resilience) associated with conventional metallic or non-metallic implants, particularly when implant techniques are optimised. Orthopaedic biomaterials' prospects (i.e., pores architectures, 3D implants, and smart biomaterials) are intriguing in achieving desired implant characteristics and structure exhibiting stimuli-responsive attitude. The primary barriers to commercialization of nanotechnology-based composites are ultimately discussed, therefore assisting in overcoming the constraints in relation to certain pre-existing orthopaedic biomaterials, critical factors such as quality, implant life, treatment cost, and pain alleviation.

Machine Learning-Assisted Sensor Array Based on Poly(amidoamine) (PAMAM) Dendrimers for Diagnosing Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, and the early diagnosis of AD remains challenging. Here we have developed a fluorescent sensor array composed of three modified polyamidoamine dendrimers. Proteins of various properties were differentiated via this array with 100% accuracy, proving the rationality of the array's design. The mechanism of the fluorescence response was discussed. Furthermore, the robust three-element array enables parallel detection of multiple Aß40/Aß42 aggregates (0.5 µM) in diverse interferents, serum media, and cerebrospinal fluid (CSF) with high accuracy, through machine learning algorithms, demonstrating the tremendous potential of the sensor array in Alzheimer's disease diagnosis.