Due to its unique advantages, which include minimal invasiveness and relative clinical safety, phototherapy is considered to be a promising approach for cancer treatment. However, the treatment efficacy of phototherapy is often restricted by the limited depth of light penetration and the low targeting effect of phototherapeutic agents. The emergence of light-responsive nanomaterials offers a possible approach to achieve enhanced phototherapy potency. This review summarizes the progress in biomedical applications of light-responsive nanomaterials for cancer therapy, which include photothermal therapy (PTT), photodynamic therapy (PDT), light-responsive molecule delivery, and light-controlled combination therapy. Future prospects are also discussed. This review aims to demonstrate the significance of light-responsive nanomaterials in cancer therapy and to provide strategies to expand the applications of phototherapy.
An appropriate cell microenvironment is key to tissue engineering and regenerative medicine. Revealing the factors that influence the cell microenvironment is a fundamental research topic in the fields of cell biology, biomaterials, tissue engineering, and regenerative medicine. The cell microenvironment consists of not only its surrounding cells and soluble factors, but also its extracellular matrix (ECM) or nearby external biomaterials in tissue engineering and regeneration. This review focuses on six aspects of biomaterial-related cell microenvironments: ① chemical composition of materials, ② material dimensions and architecture, ③material-controlled cell geometry, ④effects of material charges on cells, ⑤ matrix stiffness and biomechanical microenvironment, and ⑥ surface modification of materials. The present challenges in tissue engineering are also mentioned, and eight perspectives are predicted.
Spinal cord injury (SCI) is a tremendous disaster in a person's life. It interrupts the brain–body neuronal circuits, resulting in functional deficits. Pathogenesis of SCI is a progressive and comprehensive event. In clinical trials, attempts to promote nerve regeneration and functional recovery after SCI have met with failures. Recently, with the development of transcriptome sequencing and biomaterials, researchers have struggled to explore novel efficient therapeutic treatments for SCI. Here, we summarize the recent progress that has been made in SCI repair based on the lesion microenvironment, neural circuits, and biomaterial scaffolds. We also propose several important directions for future research, including targetedmicroRNA therapy, blood vessel interventions, and multiple treatment combinations. In short, we hope this review will enlighten researchers in the field and pave the way for SCI therapy.
Macroencapsulation has been widely used in cell therapy due to its capability to provide immune-privileged sites for implanted allogeneic or xenogeneic cells. Macroencapsulation also serve to provide mechanical and physiochemical support for maintaining cell expansion and promoting therapeutic functions. Macroencapsulation devices such as membrane-controlled release systems, hydrogels, microneedle (MN) array patches, and three-dimensional (3D) stents have shown promising in-lab and preclinical results in the maintenance of long-term cell survival and the strengthening of treatment efficacy. Recent studies focus on expanding the applications of these devices to new cell-based areas such as chimeric antigen receptor (CAR)-T cell delivery, cardiovascular disease therapy, and the exploration of new materials, construction methods, and working principles to augment treatment efficacy and prolong therapy duration. Here, we survey innovative platforms and approaches, as well as translation outcomes, for advancing the performance and applications of macrodevices for cell-based therapies. A discussion and critique regarding future opportunities and challenges is also provided.
Articular cartilage (AC) is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints. AC defects are common in the knees of young and physically active individuals. Because of the lack of suitable tissue-engineered artificial matrices, current therapies for AC defects, especially full-thickness AC defects and osteochondral interfaces, fail to replace or regenerate damaged cartilage adequately. With rapid research and development advancements in AC tissue engineering (ACTE), functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favorable biomechanical properties, water content, swelling ability, cytocompatibility, biodegradability, and lubricating behaviors. They can be rationally designed and conveniently tuned to simulate the extracellular matrix of cartilage. This article briefly introduces the composition, structure, and function of AC and its defects, followed by a comprehensive review of the exquisite (bio)design and (bio)fabrication of functionalized hydrogels for AC repair. Finally, we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation.
The occurrence of coronavirus disease 2019 (COVID-19) was followed by a small burst of cases around the world; afterward, due to a series of emergency non-pharmaceutical interventions (NPIs), the increasing number of confirmed cases slowed down in many countries. However, the lifting of control measures by the government and the public's loosening of precautionary behaviors led to a sudden increase in cases, arousing deep concern across the globe. arousing deep concern across the globe. This study evaluates the situation of the COVID-19 pandemic in countries and territories worldwide from January 2020 to February 2021. According to the time-varying reproduction number (R(t)) of each country or territory, the results show that almost half of the countries and territories in the world have never controlled the epidemic. Among the countries and territories that had once contained the occurrence, nearly half failed to maintain their prevention and control, causing the COVID-19 pandemic to rebound across the world—resulting in even higher waves in half of the rebounding countries or territories. This work also proposes and uses a time-varying country-level transmission risk score (CTRS), which takes into account both R(t)
and daily new cases, to demonstrate country-level or territory-level transmission potential and trends. Time-varying hierarchical clustering of time-varying CTRS values was used to successfully reveal the countries and territories that contributed to the recent aggravation of the global pandemic in the last quarter of 2020 and the beginning of 2021, and to identify countries and territories with an increasing risk of COVID-19 transmission in the near future. Furthermore, a regression analysis indicated that the introduction and relaxation of NPIs, including workplace closure policies and stay-at-home requirements, appear to be associated with recent global transmission changes. In conclusion, a systematic evaluation of the global COVID-19 pandemic over the past year indicates that the world is now in an unexpected situation, with limited lessons learned. Summarizing the lessons learned could help in designing effective public responses for constraining future waves of COVID-19 worldwide.
Current knowledge of the risk factors predicting the progression to severe coronavirus disease 2019 (COVID-19) among patients in community isolation who either are asymptomatic or only suffer from mild COVID-19 is very limited. Using a multivariable competing risk survival analysis, we herein identify several important predictors of progression to severe COVID-19—rather than to recovery—among patients in community isolation. A competing risk survival analysis was performed on time-to-event data from a cohort study of all COVID-19 patients (n = 1753) in the largest community isolation center in Wuhan, China, from opening to closing. The exposures were age, sex, respiratory symptoms, gastrointestinal symptoms, general symptoms, and computed tomography (CT) scan signs. The main outcomes were time to COVID-19 deterioration or recovery. The factors predicting progression to severe COVID-19 among the patients in community isolation were: male sex (hazard ratio (HR) = 1.29, 95% confidence interval (CI), 1.04–1.58, p = 0.018), young and old age, dyspnea (HR = 1.58, 95% CI, 1.24–2.01, p < 0.001), and CT signs of ground-glass opacity (HR = 1.39, 95% CI, 1.04–1.86, p = 0.024) and infiltrating shadows (HR= 1.84, 95% CI, 1.22–2.78, p = 0.004). The risk of progression was found to be lower among patients with nausea or vomiting (HR = 0.53, 95% CI, 0.30–0.96, p = 0.036) and headaches (HR = 0.54, 95% CI, 0.29–0.99, p = 0.046). Based on the results of this study, resource-poor settings, dyspnea, sex, and age can easily be used to identify mild COVID-19 patients who are at increased risk of progression. Looking for CT signs of ground-glass opacity and infiltrating shadows may be an affordable option to support triage decisions in resource-rich settings. Common and unspecific symptoms including headaches, nausea, and vomiting likely induced the selection for community isolation of COVID-19 patients who were relatively unlikely to deteriorate. Triage and prioritization outcomes could be boosted if strategies are incorporated to minimize the inefficient prioritization of harmless comorbidities.
In 2020 and 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, caused a global pandemic. Vaccines are expected to reduce the pressure of prevention and control, and have become the most effective strategy to solve the pandemic crisis. SARS-CoV-2 infects the host by binding to the cellular receptor angiotensin converting enzyme 2 (ACE2) via the receptor-binding domain (RBD) of the surface spike (S) glycoprotein. In this study, a candidate vaccine based on a RBD recombinant subunit was prepared by means of a novel glycoengineered yeast Pichia pastoris expression system with characteristics of glycosylation modification similar to those of mammalian cells. The candidate vaccine effectively stimulated mice to produce high-titer anti-RBD specific antibody. Furthermore, the specific antibody titer and virus-neutralizing antibody (NAb) titer induced by the vaccine were increased significantly by the combination of the double adjuvants Al(OH)3 and CpG. Our results showed that the virus-NAb lasted for more than six months in mice. To summarize, we have obtained a SARS-CoV-2 vaccine based on the RBD of the S glycoprotein expressed in glycoengineered Pichia pastoris, which stimulates neutralizing and protective antibody responses. A technical route for fucose-free complex-type N-glycosylation modified recombinant subunit vaccine preparation has been established.
Recently, electrospinning (ESP) has been widely used as a synthetic technology to prepare nanofibers with unique properties from various raw materials. The applications of functionalized nanofibers have gradually developed into one of the most exciting topics in the field of materials science. In this review, we focus on the preparation of multi-structure fibrous nanomaterials by means of multi-fluidic ESP and review the applications of multi-structure nanofibers in energy, catalysis, and biology. First, the working principle and process of ESP are introduced; then, we demonstrate how the microfluidic concept is combined with the ESP technique to the multi-fluidic ESP technique. Subsequently, the applications of multistructure nanofibers in energy (Li+/Na+ batteries and Li–S batteries), hetero-catalysis, and biology (drug delivery and tissue engineering) are introduced. Finally, challenges and future directions in this emerging field are summarized.
Soft biomaterials hold great potential for a plethora of biomedical applications because of their deformability, biodegradability, biocompatibility, high bioactivity, and low antigenicity. Multicomponent soft biomaterials are particularly attractive as a way of accommodating components made of different materials and generating combinative functions. Microfluidic technology has emerged as an outstanding tool in generating multicomponent materials with elaborate structures and constituents, in that it can manipulate multiphasic flows precisely on the micron scale. In recent decades, much progress has been achieved in the microfluidic fabrication of multicomponent soft biomaterials with finely defined physicochemical properties capable of controllable therapeutics delivery, three-dimensional (3D) cell culture, flexible devices and wearable electronics, and biosensing for molecules. In the paper, we summarize current progress in multicomponent soft biomaterials derived from microfluidics and emphasize their applications in biomedical fields. We also provide an outlook of the remaining challenges and future trends in this field.
The Lancang–Mekong River (LMR) is an important transboundary river that originates from the Tibetan plateau, China and flows through six nations in Southeast Asia. Knowledge about the past and future changes in climate and water for this basin is critical in order to support regional sustainable development. This paper presents a comprehensive review of the scientific progress that has been made in understanding the changing climate and water systems, and discusses outstanding challenges and future research opportunities. The existing literature suggests that: ① the warming rate in the Lancang–Mekong River basin (LMRB) is higher than the mean global warming rate, and it is higher in its upper portion, the Lancang River basin (LRB), than in its lower portion, the Mekong River basin (MRB); ② historical precipitation has increased over the LMRB, particularly from 1981 to 2010, as the wet season became wetter in the entire basin, while the dry season became wetter in the LRB but drier in the MRB; ③ in the past, streamflow increased in the LRB but slightly decreased in the MRB, and increases in streamflow are projected for the future in the LMRB; and ④ historical streamflow increased in the dry season but decreased in the wet season from 1960 to 2010, while a slight increase is projected during the wet season. Four research directions are identified as follows: ① investigation of the impacts of dams on river flow and local communities; ② implementation of a novel water–energy–food–ecology (WEFE) nexus; ③ integration of groundwater and human health management with water resource assessment and management; and ④ strengthening of transboundary collaboration in order to address sustainable development goals (SDGs).
Compared with conventional cylinder airlift bioreactors (CCABs) that produce coarse bubbles, a novel rectangular dynamic membrane airlift bioreactor (RDMAB) developed in our lab produces fine bubbles to enhance the volumetric oxygen mass transfer coefficient (kLa) and gas holdup, as well as improve the bioprocess in a bioreactor. In this study, we compared mass transfer, gas holdup, and batch and continuous fermentation for RNA production in CCAB and RDMAB. In addition, unstructured kinetic models for microbial growth, substrate utilization, and RNA formation were established. In batch fermentation, biomass, RNA yield, and substrate utilization in the RDMAB were higher than those in the CCAB, which indicates that dynamic membrane aeration produced a high kLa by fine bubbles; a higher kLa is more beneficial to aerobic fermentation. The starting time of continuous fermentation in the RDMAB was 20 h earlier than that in the CCAB, which greatly improved the biological process. During continuous fermentation, maintaining the same dissolved oxygen level and a constant dilution rate, the biomass accumulation and RNA concentration in the RDMAB were 9.71% and 11.15% higher than those in the CCAB, respectively. Finally, the dilution rate of RDMAB was 16.7% higher than that of CCAB during continuous fermentation while maintaining the same air aeration. In summary, RDMAB is more suitable for continuous fermentation processes. Developing new aeration and structural geometry in airlift bioreactors to enhance kLa and gas holdup is becoming increasingly important to improve bioprocesses in a bioreactor.
Even though switching in vacuum is a technology with almost 100 years of history, its recent developments are still changing the future of power transmission and distribution systems. First, current switching in vacuum is an eco-friendly technology compared to switching in SF6 gas, which is the strongest greenhouse gas according to the Kyoto Protocol. Vacuum, an eco-friendly natural medium, is promising for reducing the usage of SF6 gas in current switching in transmission voltage. Second, switching in vacuum achieves faster current interruption than existing alternating current (AC) switching technologies. A vacuum circuit breaker (VCB) that uses an electromagnetic repulsion actuator is able to achieve a theoretical limit of AC interruption, which can interrupt a short-circuit current in the first half-cycle of a fault current, compared to the more common three cycles for existing current switching technologies. This can thus greatly enhance the transient stability of power networks in the presence of short-circuit faults, especially for ultra- and extra-high-voltage power transmission lines. Third, based on fast vacuum switching technology, various brilliant applications emerge, which are benefiting the power systems. They include the applications in the fields of direct current (DC) circuit breakers (CBs), fault current limiting, power quality improvement, generator CBs, and so forth. Fast vacuum switching technology is promising for controlled switching technology in power systems because it has low variation in terms of opening and closing times. With this controlled switching, vacuum switching technology may change the ″gene″ of power systems, by which power switching transients will become smoother.
Humanity is facing an enormous and growing worldwide threat from the emergence of multi-drugresistant (MDR) Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Polymyxin B and E (colistin) constitute the last-line therapies for treating MDR Gram-negative bacteria. Polymyxin is a cationic antibacterial peptide that can destroy the outer membrane of Gram-negative bacteria. With the increasing clinical application of polymyxin, however, there have been many reports of the occurrence of polymyxin-resistant Gram-negative bacteria. This resistance is mainly mediated by the modification or complete loss of lipopolysaccharide (LPS). LPS is also a virulence factor of Gram-negative bacteria, and alterations of LPS may correlate with virulence. Although it is generally believed that the biological costs associated with drug resistance may enable benign susceptible bacteria to overcome resistant bacteria when antibiotic pressure is reduced, some studies have shown that polymyxin-resistant bacteria are associated with higher virulence and greater fitness compared with their susceptible counterparts. To predict the development of polymyxin resistance and evaluate interventions for its mitigation, it is important to understand the relative biological cost of polymyxin resistance compared with susceptibility. The impact of polymyxin resistance mechanisms on the virulence and fitness of these three Gram-negative bacteria are summarized in this review.
Targeted genotyping is an extremely powerful approach for the detection of known genetic variations that are biologically or clinically important. However, for non-model organisms, large-scale target genotyping in a cost-effective manner remains a major challenge. To address this issue, we present an ultrahigh-multiplex, in-solution probe array-based high-throughput diverse marker genotyping (HDMarker) approach that is capable of targeted genotyping of up to 86 000 loci, with coverage of the whole gene repertoire, in what is a 27-fold and six-fold multiplex increase in comparison with the conventional Illumina GoldenGate and original HD-Marker assays, respectively. We perform extensive analyses of various ultrahigh-multiplex levels of HD-Marker (30 k-plex, 56 k-plex, and 86 k-plex) and show the power and excellent performance of the proposed method with an extremely high capture rate (about 96%) and genotyping accuracy (about 96%). With great advantages in terms of cost (as low as 0.0006 USD per genotype) and high technical flexibility, HD-Marker is a highly efficient and powerful tool with broad application potential for genetic, ecological, and evolutionary studies of non-model organisms.
Bone defects resulting from trauma, surgery, congenital malformations, and other factors are among the most common health problems nowadays. Although current strategies such as autografts and allografts are recognized as the most successful treatments for stimulating bone regeneration, limitations such as graft source and complications still exist. SmartBone® is a xeno-hybrid bone graft (made from bovine bone matrix, poly(L-lactic-co-ε-caprolactone), and gelatin) with a positive clinical record for bone regeneration. In this study, the formulation for designing xeno-hybrid bone grafts using gelatins from different sources (bovine- and porcine-derived gelatin, with bone grafts named SBN and SPK, respectively) was investigated, and the biological responses were evaluated in vitro and in vivo. The results demonstrate that gelatins from both bovine and porcine sources can be loaded onto SmartBone® successfully and safely, withstanding the aggressive manufacturing processes. Different bone cell responses were observed in vitro. SBN was found to enhance osteocalcin secretion while SPK was found to upregulate osteopontin from human osteoblasts. In vivo, both bone grafts promoted osteogenesis, but SPK degraded earlier than SBN. Our findings suggest that SBN and SPK provide different yet comparable solutions for optimizing the bone resorption and regeneration balance. These xeno-hybrid bone grafts possess ideal potential for bone defect repairing.
The Qi Tai Telescope (QTT), which has a 110 m aperture, is planned to be the largest scale steerable telescope in the world. Ideally, the telescope's repeated pointing accuracy error should be less than 2.5 arc seconds (arcsec); thus, the telescope structure must satisfy ultra-high precision requirements. In this pursuit, the present research envisages a reverse-design method for the track surface to reduce the difficulty of the telescope's design and manufacture. First, the distribution characteristics of the test data for the track error were verified using the skewness coefficient and kurtosis coefficient methods. According to the distribution characteristics, the azimuth track error was simulated by a two-scale model. The error of the long period and short amplitude was characterized as large-scale and described by a trigonometric function, while the short period and high amplitude error was characterized as small-scale and simulated by a fractal function. Based on the two-scale model, effect of the error on the pointing accuracy was deduced. Subsequently, the relationship between the root mean square (RMS) of the track error and the RMS of the pointing accuracy error of the telescope was deduced. Finally, the allowable RMS value of the track error was derived from the allowable pointing accuracy errors. To validate the effectiveness of the new design method, two typical radio telescopes (the Green Bank Telescope (GBT) and the Large Millimeter Telescope (LMT)) were selected as experimental examples. Through comparison, the theoretical calculated values of the pointing accuracy of the telescope were consistent with the measured values, with a maximum error of less than 10%.Graphical abstractQi Tai Telescope (QTT) with a 110 m caliber, it will become the largest scale steerable telescope in the world. Its repeated pointing accuracy error should be less than 2.5 arc seconds and the telescope structure must satisfy an ultra-high precision requirements. To reduce the difficulty of telescope's design and manufacture, a reverse design method of the track surface was proposed. Firstly, the distribution characteristics of the test data of track error were verified using the skewness coefficient and kurtosis coefficient methods. According to the distribution characteristics, the azimuth track error was simulated by a two scales model. The error of long-period-short-amplitude was defined as the large scale, which was described by the trigonometric function. The short-period-high-amplitude error was recognized as the small scale, and simulated by the fractal function. Based on the two scales model, effect of it on the pointing accuracy was deduced. And then the relationship between the RMS (Root Mean Square) of track error and the RMS value of the telescope's pointing accuracy errors was deduced. Finally, the allowable RMS value of track error was derived from the allowable pointing accuracy errors. To validate the effectiveness of the new design method, two typical radio telescopes (the Green Bank Telescope and the Large Millimeter Telescope) were selected as experimental examples. Through comparison, the theoretical calculated values of the telescope's pointing accuracy are in good agreement with the measured values, with a maximum error less than 10%.
Microbially induced calcium carbonate (CaCO3) precipitation (MICP) has been investigated as a sustainable alternative to conventional concrete remediation methods for improving the mechanical properties and durability of concrete structures. To date, urea-dependent MICP is the most widely employed MICP pathway in biological self-healing concrete research as its use has resulted in efficient CaCO3 precipitation rates. NH3 is a byproduct of ureolysis, and can be hazardous to cementitious structures and the health of various species. Accordingly, non-ureolytic bacterial concrete self-healing systems have been developed as eco-friendly alternatives to urea-dependent self-healing systems. Non-ureolytic pathways can improve the physical properties of concrete samples and incorporate the use of waste materials; they have the potential to be cost-effective and sustainable. Moreover, they can be applied in terrestrial and marine environments. To date, research on non-ureolytic concrete self-healing systems has been scarce compared to that on ureolytic systems. This article discusses the advances and challenges in non-ureolytic bacterial concrete self-healing studies and highlights the directions for future research.
The rapidly increasing demand for wearable electronic devices has motivated research in low-cost and flexible printed batteries with diverse form factors and architectures. In the past, technological achievements in the field have been emphasized, overlooking the industrial and market requirements. However, different applications require different battery chemistries and formats, that greatly impacts the manufacturing process and competition landscape. These chemistries and formats should therefore be selected carefully to maximize the chances for commercial success. As some of these technologies are starting to be marketed for portable electronics, there is a pressing need to evaluate different printing technologies and compare them in terms of the processing constraints and product requirements of specific electronic devices. By evaluating the intrinsic strengths and current limitations of printed battery technologies, development pathways can be prioritized, and potential bottlenecks can be overcome to accelerate the path to market.