Search

Throughout billions of years, biological systems have evolved sophisticated, multiscale hierarchical structures to adapt to changing environments. Biomaterials are synthesized under mild conditions through a bottom-up self-assembly process, utilizing substances from the surrounding environment, and meanwhile are regulated by genes and proteins. Additive manufacturing, which mimics this natural process, provides a promising approach to developing new materials with advantageous properties similar to natural biological materials. This review presents an overview of natural biomaterials, emphasizing their chemical and structural compositions at various scales, from the nanoscale to the macroscale, and the key mechanisms underlying their properties. Additionally, this review describes the designs, preparations, and applications of bioinspired multifunctional materials produced through additive manufacturing at different scales, including nano, micro, micro-macro, and macro levels. The review highlights the potential of bioinspired additive manufacturing to develop new functional materials and insights into future directions and prospects in this field. By summarizing the characteristics of natural biomaterials and their synthetic counterparts, this review inspires the development of new materials that can be utilized in various applications.

Previous studies have shown that attention influences audiovisual integration (AVI) in multiple stages, but it remains unclear how AVI interacts with attentional load. In addition, while aging has been associated with sensory-functional decline, little is known about how older individuals integrate cross-modal information under attentional load. To investigate these issues twenty older adults and 20 younger adults were recruited to conduct a dual task including a multiple object tracking (MOT) task, which manipulated sustained visual attentional load, and an audiovisual discrimination task, which assesses AVI. The results showed that response times were shorter and hit rate was higher for audiovisual stimuli than for auditory or visual stimuli alone and in younger adults than in older adults. The race model analysis showed that AVI was higher under the load_3 condition (monitoring two targets of the MOT task) than under any other load condition (no-load [NL], one or three targets monitoring). This effect was found regardless of age. However, AVI was lower in older adults than younger adults under NL condition. Moreover, the peak latency was longer, and the time window of AVI was delayed in older adults compared to younger adults under all conditions. These results suggest that slight visual sustained attentional load increased AVI but that heavy visual sustained attentional load decreased AVI, which supports the claim that attention resource was limited, and we further proposed that AVI was positively modulated by attentional resource. Finally, there were substantial impacts of aging on AVI; AVI was delayed in older adults.

The hierarchical structures of biological materials endow them with excellent mechanical performance and specific functionality. Interestingly, structures are formed under the functions of biological systems under mild conditions, which inspires the synthesis and fabrication of artificial materials at room temperature. During the formation of biological structures, biotemplating effects play critical roles, such as confined environments, surface functional groups, molecular conformation, and self-assembly behavior. Based on these functional characteristics, many studies have focused on choosing biological templates that are abundant in nature and easy to obtain or to design customized biological templates based on pristine biotemplates to realize the formation of organized structures and the optimized performance of materials. In this review, we summarize the four types of biotemplates, including collagen, cellulose, viruses, and bacteria, for the synthesis of organized structures. Benefiting from this review, the effects of biotemplating on artificial material synthesis will receive more attention from researchers and will contribute to the synthesis of new materials and structures.

Collagen fibrils hierarchically assemble from microscale to macroscale, which endows the natural composite bone with good mechanical properties and remodeling functions. Revealing the intrafibrillar growth process of hydroxyapatite nanocrystals of collagen will guide the research of bone repair or collagen-based composites. Herein, we investigated the mineralization of multiscale collagen matrices and strongly proved the intrafibrillar hydroxyapatite nanocrystals in the collagen fibrils. The hydroxyapatite nanocrystals were deposited within collagen fibrils with co-orientation along the (002) crystal plane, which is the longitude of the fibril. The whole growth process was captured by TEM to demonstrated the five stages of the intrafibrillar growth process of hydroxyapatite nanocrystals. The infiltration and transformation of amorphous calcium phosphate in isolated collagen fibrils are both demonstrated. The intrafibrillar growth process of hydroxyapatite nanocrystals in collagen film was also investigated, showing that the growth area of collagen films increased linearly with time and the growth process. By studying the in situ mineralization under different reaction conditions, the kinetic equation of the mineralized area of collagen film under each condition was obtained, and the optimal hydroxyapatite mineralized solution was proved to be a solution with polyacrylic acid of 50 μG/mL and a pH of 7.5. Our work provides more detailed information of the growth process of HAP nanocrystals during the mineralization of collagen at different scales and would contribute to future research on the formation process of more minerals in collagen.

Abstract A reduction in the particle size is expected to improve the properties and increase the application potential of high-entropy alloys. Therefore, in this study, a novel sol–gel autocombustion technique was first used to synthesize high-entropy alloys. The average grain size of the prepared nanocrystalline CoCrCuNiAl high-entropy alloys showed was 14 nm with an excellent and uniform dispersion, exhibiting a distinct magnetic behavior similar to the superparamagnetic behavior. We show that the metal nitrates first form (Co,Cu,Mg,Ni,Zn)O high-entropy oxides, and then in situ reduce to CoCrCuNiAl high-entropy alloys by the reducing gases, and the chelation between citric acid and the metal ions and the in situ chemical reactions are the dominant reaction mechanisms. We demonstrate that the sol–gel autocombustion process is an efficient way to synthesize solid solution alloys eluding the restriction of a high mixing entropy.

In living organisms, confined space with specific chemical composition and elaborate spatial distribution regulates the formation of natural structures. Learning from the natural structure-forming process, novel synthesis approaches in deliberated confined systems have been proposed for obtaining designed structures. Artificial confined systems can effectively regulate the synthesis of materials with defined structures according to the geometry of confinements. Collagen fibrils provide biological confinements for the formation of hierarchical structure with periodic arrangement. Genetically engineered living organisms with designed confinements can direct the synthesis of three-dimensional nanostructures. More novel structures will be rationally fabricated in the future with the aid of deeper understanding of biological processes.

Carbon fiber is mainly distributed in the shape of short fibers and continuous fiber bundles as the reinforcing phase in metal matrix composites, and it is seldom studied as braided rope shaped to reinforce the matrix. For this paper, the pretreatment and the surface metallization of the carbon fiber braided rope were studied. Besides, the casting experiments of aluminum-based carbon fiber braided rope composites were performed without external pressure. XPS analysis shows that the surface of the carbon fiber braided rope treated with ultrasonic degumming contains many hydrophilic oxygen-containing functional groups C-OH, C=O, COOH, etc., which can effectively improve the wettability between the carbon fiber braided rope and the aluminum matrix. SEM, EDS, and XRD were used to analyze the micromorphology and structure of the copper plating on the surface of carbon fiber braided ropes obtained from different pH plating solutions. When pH is 12, a continuous, uniform, and dense layer was formed on the surface of carbon fiber braided ropes. In addition, copper coating can effectively inhibit the formation of Al4C3 brittle phase. Finally, the mechanical properties results indicated that the tensile strength of the carbon fiber bundle and carbon fiber rope reinforced composite materials were 69 MPa and 83 MPa, respectively, indicating that the reinforcing effect of the carbon fiber rope is better than that of the carbon fiber bundle.

Objectives: In the winter of 2013, people were facing the risk of human-to-human transmission of the re-emerging influenza A(H7N9) virus. We report herein information on the clinical features of two patients from the same family infected with this virus, the genomic sequences of the viruses harbored, and antiviral drug sensitivity. Methods: Clinical and epidemiological data of two patients from the same family were collected and analyzed. Sequencing was done for the viruses isolated from these two patients and one epidemiologically related chicken, and the sequences of the eight gene segments of the viruses were analyzed phylogenetically. The sensitivity of the viruses to antiviral drug treatment was determined by neuraminidase inhibitor susceptibility test. Results: The two patients from one family cluster shared the same symptoms but had different outcomes, and had a strong epidemiological link. Three strains, two from these two patients and one from the chicken, were isolated. Genome sequencing and analyses of phylogenetic trees demonstrated that the two viruses were almost identical. We noted the presence of the PB2 E627K amino acid substitution that was not present in isolates from the first wave, as well as two new mutations in the NA gene and six in the PB2 gene. Drug sensitivity testing showed that the new isolates were resistant to oseltamivir but sensitive to peramivir. Conclusions: The two patients from one family cluster were probable human-to-human transmission cases. The new isolates were sensitive to peramivir but showed reduced sensitivity to oseltamivir.

Background: Corona Virus Disease 2019(COVID-19)is a global pandemic novel coronavirus infection disease caused by Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Although rapid, large-scale testing plays an important role in patient management and slowing the spread of the disease. However, there has been no good and widely used drug treatment for infection and transmission of SARS-CoV-2. Key findings: Therefore, this review updates the body of knowledge on viral structure, infection routes, detection methods, and clinical treatment, with the aim of responding to the large-section caused by SARS-CoV-2. This paper focuses on the structure of SARS-CoV-2 viral protease, RNA polymerase, serine protease and main proteinase-like protease as well as targeted antiviral drugs. Conclusion: In vitro or clinical trials have been carried out to provide deeper thinking for the pathogenesis, clinical diagnosis, vaccine development and treatment of SARS-CoV-2.

Host-virus interactions can significantly impact the viral life cycle and pathogenesis; however, our understanding of the specific host factors involved in highly pathogenic avian influenza A virus H7N9 (HPAI H7N9) infection is currently restricted. Herein, we designed and synthesized 65 small interfering RNAs targeting host genes potentially associated with various aspects of RNA virus life cycles. Afterward, HPAI H7N9 viruses were isolated and RNA interference was used to screen for host factors likely to be involved in the life cycle of HPAI H7N9. Moreover, the research entailed assessing the associations between host proteins and HPAI H7N9 proteins. Twelve key host proteins were identified: Annexin A (ANXA)2, ANXA5, adaptor related protein complex 2 subunit sigma 1 (AP2S1), adaptor related protein complex 3 subunit sigma 1 (AP3S1), ATP synthase F1 subunit alpha (ATP5A1), COPI coat complex subunit alpha (COP)A, COPG1, heat shock protein family A (Hsp70) member 1A (HSPA)1A, HSPA8, heat shock protein 90 alpha family class A member 1 (HSP90AA1), RAB11B, and RAB18. Co-immunoprecipitation revealed intricate interactions between viral proteins (hemagglutinin, matrix 1 protein, neuraminidase, nucleoprotein, polymerase basic 1, and polymerase basic 2) and these host proteins, presumably playing a crucial role in modulating the life cycle of HPAI H7N9. Notably, ANXA5, AP2S1, AP3S1, ATP5A1, HSP90A1, and RAB18, were identified as novel interactors with HPAI H7N9 proteins rather than other influenza A viruses (IAVs). These findings underscore the significance of host-viral protein interactions in shaping the dynamics of HPAI H7N9 infection, while highlighting subtle variations compared with other IAVs. Deeper understanding of these interactions holds promise to advance disease treatment and prevention strategies.

ABSTRACTThe H7N9 virus mutated in 2017, resulting in new cases of highly pathogenic avian influenza (HPAI) H7N9 virus infection. H7N9 was found in a viraemic patient in Guangdong province, China. The present study aimed to clarify the pathogenic characteristics of HPAI H7N9. Virus was isolated from the plasma and sputum of the patient with HPAI H7N9. Liquid phase chip technology was used to detect the plasma cytokines from the infected patient and healthy controls. Mice were infected with strains A/Guangdong/GZ8H002/2017(H7N9) and A/Zhejiang/DTID-ZJU01/2013(H7N9) to observe the virus’s pathogenic characteristics. Serum and brain tissue were collected at 2, 4, and 6 days after infection. The viruses in serum and brain tissue were detected and isolated. The two strains were infected into A549 cells, exosomes were extracted, and virus genes in the exosomes were assessed. Live virus was isolated from the patient’s plasma. An acute cytokine storm was detected during the whole course of the disease. In animal experiments, A/Guangdong/GZ8H002/2017(H7N9) was more pathogenic than A/Zhejiang /DTID-ZJU01/2013(H7N9) and resulted in the death of mice. Live virus was isolated from infected mouse serum. Virus infection was also detected in the brain of mice. Under viral stress, A549 cells secreted exosomes containing the entire viral genome. The viraemic patient was confirmed to have an HPAI H7N9 infection. A/Guangdong/GZ8H002/2017(H7N9) showed significantly enhanced toxicity. Patient deaths might result from cytokine storms and brain infections. Extrapulmonary tissue infection might occur via the exosome pathway. The determined pathogenic characteristics of HPAI H7N9 will contribute to its future treatment.

The recepteur d’origine nantais (RON) receptor tyrosine kinase, belonging to the mesenchymal-to-epithelial transition proto-oncogene family, has been implicated in the pathogenesis of cancers derived from the colon, lung, breast, and pancreas. These findings lay the foundation for targeting RON for cancer treatment. However, development of RON-targeted therapeutics has not gained sufficient attention for the last decade. Although therapeutic monoclonal antibodies (TMABs) targeting RON have been validated in preclinical studies, results from clinical trials have met with limited success. This outcome diminishes pharmaceutical enthusiasm for further development of RON-targeted therapeutics. Recently, antibody–drug conjugates (ADCs) targeting RON have drawn special attention owing to their increased therapeutic activity. The rationale for developing anti-RON ADCs is based on the observation that cancer cells are not sufficiently addicted to RON signaling for survival. Thus, TMAB-mediated inhibition of RON signaling is ineffective for clinical application. In contrast, anti-RON ADCs combine a target-specific antibody with potent cytotoxins for cancer cell killing. This approach not only overcomes the shortcomings in TMAB-targeted therapies but also holds the promise for advancing anti-RON ADCs into clinical trials. In this review, we discuss the latest advancements in the development of anti-RON ADCs for targeted cancer therapy including drug conjugation profile, pharmacokinetic properties, cytotoxic effect in vitro , efficacy in tumor models, and toxicological activities in primates.

RON (recepteur d'origine nantais) and MET (hepatocyte growth factor receptor) are tyrosine kinase receptors. Various cancers have aberrant RON and MET expression and activation, which contribute to cancer cell proliferation, invasiveness, and metastasis. Here, we explored RON and MET expression in pancreatic cancer and their relationship with overall survival (OS) time, and evaluated their significance as therapeutic targets of tyrosine kinase inhibitors in pancreatic cancer. We enrolled 227 patients with pancreatic cancer in the study. RON and MET expression was analyzed by immunohistochemical staining. Four human pancreatic cancer cell lines expressing variable levels of RON or MET and four MET superfamily inhibitors (BMS777607, PHA665752, INCB28060, Tivantinib) were used. The effect of the four tyrosine kinase inhibitors on cell viability, migration, and apoptosis were determined using cell viability, scratch wound healing, and Caspase-Glo 3/7 assays. Cellular signaling was analyzed by immunoprecipitation and western blotting. The therapeutic efficacy of the tyrosine kinase inhibitors was determined with mouse xenograft pancreatic cancer models in vivo. There was wide aberrant RON and MET expression in the cancer tissues. In 227 pancreatic cancer samples, 33% had RON overexpression, 41% had MET overexpression, and 15.4% had RON and MET co-overexpression. RON and MET expression were highly correlated. RON and MET expression levels were significantly related to OS. Patients with RON and MET co-overexpression had poorer OS. BMS777607 and PHA665752 inhibited pancreatic cancer cell viability and migration, and promoted apoptosis by inhibiting RON and MET phosphorylation and further inhibiting the downstream signaling pathways in vitro. They also inhibited tumor growth and further inhibited phosphorylated (phosphor)-RON and phospho-MET expression in the mouse xenograft models in vivo effectively. INCB28060, which inhibits the MET signaling pathway alone, was not effective. RON and MET can be important indicators of prognosis in pancreatic cancer. Tyrosine kinase inhibitors targeting RON and MET in pancreatic cancer are a novel and potential approach for pancreatic cancer therapy.