Engineering Cardiac Tissue for Advanced Heart-On-A-Chip Platforms.

Cardiovascular disease is a major cause of mortality worldwide, and current preclinical models including traditional animal models and 2D cell culture models have limitations in replicating human native heart physiology and response to drugs. Heart-on-a-chip (HoC) technology offers a promising solution by combining the advantages of cardiac tissue engineering and microfluidics to create in vitro 3D cardiac models, which can mimic key aspects of human microphysiological systems and provide controllable microenvironments. Herein, recent advances in HoC technologies are introduced, including engineered cardiac microtissue construction in vitro, microfluidic chip fabrication, microenvironmental stimulation, and real-time feedback systems. The development of cardiac tissue engineering methods is focused for 3D microtissue preparation, advanced strategies for HoC fabrication, and current applications of these platforms. Major challenges in HoC fabrication are discussed and the perspective on the potential for these platforms is provided to advance research and clinical applications.

Photocurable injectable Janus hydrogel with minimally invasive delivery for all-in-one treatment of gastric perforations and postoperative adhesions.

Background: Surgical sutures for sealing gastric perforations (GP) are associated with severe inflammation and postoperative adhesions. Hydrogel bioadhesives offer a potential alternative for sutureless repair of GP; however, their application in minimally invasive surgery is limited due to their prefabricated patch-form, lacking in situ gelation capability. In this study, we emphasized an all-in-one minimally invasive strategy for sutureless repair of acute GP. Methods: an injectable photocurable Janus hydrogel was synthesized, and their ability to seal GP was performed. A rat GP model was used to verify the wound healing and antiadhesion efficiency of hydrogels, and a rabbit GP model was used to verify their laparoscopic feasibility. A fresh human corpse GP model was further employed to verify the user-friendliness of a minimally invasive deliverable (MID) device. A minipig GP model was utilized to evaluate the all-in-one minimally invasive strategy for the treatment of acute GP. Results: Such injectable Janus hydrogel exhibited asymmetric adhesiveness, where the inner-facing side of the hydrogel displays strong sealing and wound healing abilities for GP, while the outward-facing side prevents postoperative adhesion formation. We further developed a minimally invasive deliverable (MID) device integrating hydrogel-delivery parts and photocrosslinking-gelation parts in a laparoscope system. The precise delivery and rapid fluid-tight sealing process of the injectable Janus hydrogel using the MID device for in situ GP repair were demonstrated in a simulated clinical scenario. The in vivo effectiveness of GP sutureless repair was successfully validated in porcine models, with further exploration of the underlying mechanism. Conclusions: Our findings reveal that the injectable Janus hydrogel offers an all-in-one strategy for sutureless GP repair and concurrent prevention of postoperative adhesion formation by incorporating the MID device in minimally invasive surgery, presenting the significant potential to reduce patient surgical complications.

Association of selenium profile with neutralizing antibody response to inactivated SARS-CoV-2 vaccination.

BACKGROUND: Selenium profile has been related with humoral immune response after vaccination, but evidence with regard to inactivated SARS-CoV-2 vaccine is lacking. OBJECTIVE: The current study aimed to examine the relationship between selenium profile and neutralizing antibody response to inactivated SARS-CoV-2 vaccine. METHODS: Plasma selenium and selenoprotein P concentrations, neutralizing antibody against the wild-type and Omicron variant were measured at baseline and at 14 days, 98 days after the third dose of inactivated SARS-CoV-2 vaccine. RESULTS: Neutralizing antibody against the wild-type and Omicron variant increased significantly after the third vaccination dose. Both higher plasma selenium and selenoprotein P were associated with increased neutralizing antibody against the wild-type strain at baseline. Moreover, higher plasma selenoprotein P was associated with increased neutralizing antibody against Omicron variant at baseline. However, nonsignificant association were observed after the third vaccine dose. CONCLUSION: Higher selenium profile was associated with neutralizing antibody response before the third dose of inactivated SARS-CoV-2 vaccine, but not after the third dose. Further prospective cohort studies are warranted to confirm our findings.

Neural stem cell-derived exosomes-loaded adhesive hydrogel controlled-release promotes cerebral angiogenesis and neurological function in ischemic stroke.

OBJECTIVE: Ischemic stroke has become one of the leading diseases for international death, which brings burden to the economy and society. Exosomes (Exos) derived following neural stem cells (NSCs) stimulation promote neurogenesis and migration of NSCs. However, Exos themselves are easily to be removed in vivo. Our study is to investigate whether adhesive hyaluronic acid (HAD) hydrogel loading NSCs-derived-Exo (HAD-Exo) would promote the recovery of ischemic stroke. METHODS: A mouse model of middle cerebral artery occlusion (MCAO) was established. PBS, Exo, HAD, and HAD-Exo groups were independently stereotactically injected in mice, respectively. The modified neurological severity score scale and behaviour tests were used to evaluate neurological improvement. Neuroimagings were used to observe the improvement of cerebral infarct volume and vessels. Immunofluorescence staining was used to verify the expression of vascular and cell proliferation-related proteins. RESULTS: The structural and mechanical property of HAD and HAD-Exo were detected. Behavioral results showed that HAD-Exo significantly improved neurological functions, especially motor function. Neuroimagings showed that HAD-Exo significantly promoted infarct volume and angiogenesis. Immunofluorescence staining showed that HAD-Exo significantly promoted the cerebral angiogenesis and anti-inflammation. CONCLUSION: NSCs derived exosomes-loaded adhesive HAD hydrogel controlled-release could promote cerebral angiogenesis and neurological function for ischemic stroke.

A Comprehensive Evaluation of Tomato Fruit Quality and Identification of Volatile Compounds.

Tomatoes (Lycopersicon esculentum) are the most valuable vegetable crop in the world. This study identified the morphological characteristics, vitamin content, etc., from 15 tomato varieties in total, that included five each from the three experimental types, during the commercial ripening period. The results showed that the hardness with peel and the moisture content of tasty tomatoes were 157.81% and 54.50%, and 3.16% and 1.90% lower than those of regular tomatoes and cherry tomatoes, respectively, while the soluble solids were 60.25% and 20.79% higher than those of the latter two types. In addition, the contents of vitamin C, lycopene, fructose, glucose, and total organic acids of tasty tomatoes were higher than those of regular tomatoes and cherry tomatoes. A total of 110 volatile compounds were detected in the 15 tomato varieties. The average volatile compound content of tasty tomatoes was 57.94% higher than that of regular tomatoes and 15.24% higher than that of cherry tomatoes. Twenty of the 34 characteristic tomato aroma components were identified in tasty tomatoes, with fruity and green being the main odor types. Ten characteristic aroma components in regular tomatoes were similar to those of tasty tomatoes; ten types of cherry tomatoes had floral and woody aromas as the main odor types. The flavor sensory score was significantly positively correlated with the content of soluble solids, fructose, glucose, citric acid, fumaric acid, and ß-ionone (p < 0.01), and significantly negatively correlated with water content and firmness without peel. Regular, tasty, and cherry tomatoes were separated using principal component analysis, and the quality of tasty tomatoes was found to be better than cherry tomatoes, followed by regular tomatoes. These results provide valuable information for a comprehensive evaluation of fruit quality among tomato varieties to develop consumer guidelines.

Robust Kramers-Kronig holographic imaging with Hilbert-Huang transform.

Holography based on Kramers-Kronig relations (KKR) is a promising technique due to its high-space-bandwidth product. However, the absence of an iterative process limits its noise robustness, primarily stemming from the lack of a regularization constraint. This Letter reports a generalized framework aimed at enhancing the noise robustness of KKR holography. Our proposal involves employing the Hilbert-Huang transform to connect the real and imaginary parts of an analytic function. The real part is initially processed by bidimensional empirical mode decomposition into a series of intrinsic mode functions (IMFs) and a residual term. They are then selected to remove the noise and bias terms. Finally, the imaginary part can be obtained using the Hilbert transform. In this way, we efficiently suppress the noise in the synthetic complex function, facilitating high-fidelity wavefront reconstruction using ∼20% of the exposure time required by existing methods. Our work is expected to expand the applications of KKR holography, particularly in low phototoxicity biological imaging and other related scenarios.

Injectable photocurable Janus hydrogel delivering hiPSC cardiomyocyte-derived exosome for post-heart surgery adhesion reduction.

Postsurgical pericardial adhesions pose increased risks of sequelae, prolonged reoperation time, and reduced visibility in the surgical field. Here, we introduce an injectable Janus hydrogel, which exhibits asymmetric adhesiveness properties after photocrosslinking, sustained delivering induced pluripotent stem cell-derived cardiomyocyte exosomes (iCM-EXOs) for post-heart surgery adhesion reduction. Our findings reveal that iCM-EXOs effectively attenuate oxidative stress in hydrogen peroxide-treated primary cardiomyocytes by inhibiting the activation of the transcription factor nuclear factor erythroid 2-related factor 2. Notably, in rat cardiac postsurgery models, the Janus hydrogels loaded with iCM-EXOs demonstrate dual functionality, acting as antioxidants and antipericardial adhesion agents. These hydrogels effectively protect iCM-EXOs from GATA6+ cavity macrophage clearance by inhibiting the recruitment of macrophages from the thoracic cavity. These results highlight the promising potential of iCM-EXO-laden Janus hydrogels for clinical safety and efficacy validation in trials involving heart surgery patients, with the ultimate goal of routine administration during open-heart surgeries.

Multiscale Anisotropic Scaffold Integrating 3D Printing and Electrospinning Techniques as a Heart-on-a-Chip Platform for Evaluating Drug-Induced Cardiotoxicity.

Cardiac safety assessments are significant in drug discovery, as drug-induced cardiotoxicity (DIC) is the primary cause of drug attrition. Despite heart-on-a-chip (HoC) technology becoming an increasingly popular tool for evaluating DIC, its development remains a challenge owing to the anisotropic cardiac structure of the native myocardium. Herein, an anisotropic multiscale cardiac scaffold is presented via a hybrid biofabrication method by combining 3D printing with electrospinning technology, where the 3D-printed micrometer-scale scaffold frames enable mimicking the interwoven myocardium anatomical structure and the branched-aligned electrospun nanofibers network is able to directionally guide cellular arrangements. The in vitro 3D bioengineered cardiac tissues are then fabricated by encapsulating three-layer multiscale scaffolds within a photocurable methacrylated gelatin hydrogel shell. It is demonstrated that such an anisotropic multiscale structure could contribute to enhancing cardiomyocyte maturation and synchronous beating behavior. More attractively, with the integration of 3D bioengineered cardiac tissues and a self-designed microfluidic perfusion system, a 3D anisotropic HoC platform is established for evaluating DIC and cardioprotective efficacy. Collectively, these results indicate that the HoC model developed by integrating the 3D bioengineered cardiac tissues could effectively recapitulate the clinical manifestations, thereby highlighting their efficacy as a valuable preclinical platform for testing drug efficacy and cardiotoxicity.

Fatigue of an Aluminum Foam Sandwich Formed by Powder Metallurgy.

In this paper, an aluminum foam sandwich (AFS) was prepared by the rolling composite-powder metallurgy method, and its fatigue properties were studied. It was compared with an AFS made by the adhesive method to study its fatigue properties more directly. In this experiment, the fatigue performance was investigated by studying the microscopic interface, fatigue life, deflection curve, and failure mode. The results show that the fatigue life of an AFS with the rolling composite-powder metallurgy method is much longer than that with the adhesive method. The failure mode of an AFS made by the rolling composite-powder metallurgy method is shear failure, and that of an AFS made by the adhesive method is shear failure and interface debonding. An AFS with the rolling composite-powder metallurgy method has better fatigue properties. This paper also explored the fatigue damage model using the fatigue modulus method, and the polynomial fitting method has a higher fitting degree.

Injectable remote magnetic nanofiber/hydrogel multiscale scaffold for functional anisotropic skeletal muscle regeneration.

Developing an injectable anisotropic scaffold with precisely topographic cues to induce 3D cellular organization plays a critical role in volumetric muscle loss (VML) repair in vivo. However, controlling aligned myofiber regeneration in vivo based on previous injectable scaffolds continues to prove challenging, especially in a 3D configuration. Herein, we prepare the monodisperse remote magnetic controlled short nanofibers (MSNFs) with a high yield using an advanced coaxial electrospinning-cyrocutting method. An injectable anisotropic MSNF/Gel nanofiber/hydrogel scaffold based on MSNFs within photocurable hydrogel is further designed, showing the ability to guide 3D cellular alignment and organization by the precise microarchitecture control via a remote magnetic field. MSNF/Gel anisotropic scaffolds were able to recreate the macroscale and microscale topographical features of orbicular muscle and bipennate muscle mimicking their anatomical locations. Furthermore, the resultant MSNF/Gel anisotropic scaffolds significantly enhanced aligned myofiber formation in vivo and improved functional recovery of injured muscles in animal VML models. In summary, this approach offers a new promising tissue engineering strategy not only for the aligned myofiber formation for enhancing skeletal muscle regeneration in vivo but also for other biofabrication of living constructs containing complex anisotropy in vitro.

Bis (2-ethylhexyl)-2,3,4,5-tetrabromophthalate showed poor penetrability but increased the permeability of blood brain barrier: Evidences from in vitro and in vivo studies.

Bis(2ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a replacement for restricted flame retardants, has become ubiquitous in the environment. To reveal the neurotoxicity and underlying mechanism of TBPH, we first evaluated its penetrability through the blood-brain barrier (BBB) using hCMEC/D3 cells as in vitro model, and found TBPH had poor penetrability through BBB with a maximum Papp of 14.8 × 10-6 cms-1. Further study using transgenetic zebrafish (Tg flk1: EGFP) as in vivo model confirmed that TBPH could affect the BBB permeability, probably via affecting the transcription of genes encoding tight junction proteins. Finally, wild type zebrafish embryos/larvae were exposed to TBPH to evaluate the neurotoxicity. The neurodevelopment, neurotransmitters and locomotor activity of zebrafish larvae did not changed, which may be because TBPH can hardly cross the BBB to pose direct exposure to the central nervous system. However, the transcription of opsins genes and visual response to light stimulation in zebrafish larvae were inhibited, pointing to additional mechanism that may cause visual impairment indirectly. Above all, these results can help further understand the neurotoxicity and underlying mechanism by TBPH, and also pointed out potential risk of this chemical to aquatic organisms.

The impact of the COVID-19 pandemic on the demand for density: Evidence from the U.S. housing market.

We study the impact of the COVID-19 pandemic on the location demand for housing. We find that the pandemic has led to a shift in housing demand away from neighborhoods with high population density. The reduced demand for density is driven partially by the diminished need for living close to telework-compatible jobs and the declining value of access to consumption amenities. Neighborhoods with high pre-COVID-19 home values also see a greater drop in housing demand. Moreover, we find a significant shift in housing demand away from large cities, though the magnitude is smaller.

3D bioprinting in cardiac tissue engineering.

Heart disease is the main cause of death worldwide. Because death of the myocardium is irreversible, it remains a significant clinical challenge to rescue myocardial deficiency. Cardiac tissue engineering (CTE) is a promising strategy for repairing heart defects and offers platforms for studying cardiac tissue. Numerous achievements have been made in CTE in the past decades based on various advanced engineering approaches. 3D bioprinting has attracted much attention due to its ability to integrate multiple cells within printed scaffolds with complex 3D structures, and many advancements in bioprinted CTE have been reported recently. Herein, we review the recent progress in 3D bioprinting for CTE. After a brief overview of CTE with conventional methods, the current 3D printing strategies are discussed. Bioink formulations based on various biomaterials are introduced, and strategies utilizing composite bioinks are further discussed. Moreover, several applications including heart patches, tissue-engineered cardiac muscle, and other bionic structures created via 3D bioprinting are summarized. Finally, we discuss several crucial challenges and present our perspective on 3D bioprinting techniques in the field of CTE.

Occurrence and risk assessment of pharmaceuticals and personal care products (PPCPs) against COVID-19 in lakes and WWTP-river-estuary system in Wuhan, China.

The consumption of pharmaceuticals and personal care products (PPCPs) for controlling and preventing the COVID-19 would have sharply increased during the pandemic. To evaluate their post-pandemic environmental impacts, five categories of drugs were detected in lakes and WWTP-river-estuary system near hospitals of Jinyintan, Huoshenshan and Leishenshan in the three regions (J, H and L) (Regions J, H and L) in Wuhan, China. The total amount of PPCPs (ranging from 2.61 to 1122 ng/L in water and 0.11 to 164 ng/g dry weight in sediments) were comparable to historical reports in Yangtze River basin, whereas the detection frequency and concentrations of ribavirin and azithromycin were higher than those of historical studies. The distribution of concerned drugs varied with space, season, media and water types: sampling sites located at WWTPs-river-estuary system around two hospitals (Regions L and J) usually had relatively high waterborne contamination levels, most of which declined in autumn; lakes had relatively low waterborne contamination levels in summer but increased in autumn. The potential risks of detected PPCPs were further evaluated using the multiple-level ecological risk assessment (MLERA): sulfamethoxazole and azithromycin were found to pose potential risks to aquatic organisms according to a semi-probabilistic approach and classified as priority pollutants based on an optimized risk assessment. In general, the COVID-19 pandemic did not cause serious pollution in lakes and WWTPs-river-estuary system in Wuhan City. However, the increased occurrence of certain drugs and their potential ecological risks need further attention. A strict source control policy and an advanced monitoring and risk warning system for emergency response and long-term risk control of PPCPs is urgent.

Embryonic exposure to pentabromobenzene inhibited the inflation of posterior swim bladder in zebrafish larvae.

The emerging flame retardants pentabromobenzene (PBB) has been frequently detected in recent years and may pose exposure risks to wild animals and human beings. In this study, the inflation of posterior swim bladder of zebrafish larvae was used as an endpoint to study the developmental toxicity and putative mechanisms associated with PBB toxicity. Our results showed that embryonic exposure to PBB could significantly inhibit the inflation of posterior swim bladders. Reduced T3 levels and transcriptional changes of crh and pomc were observed in PBB treated zebrafish larvae at 120 hpf. However, key regulators of thyroid and adrenocortical system involved in the synthesis (tsh), biological conversion (ugt1ab, dio2) and functional regulation (trα, trß, gr) showed no significant changes. Further data revealed that prlra was the only gene that was altered among the detected genes at 96 h post fertilization (hpf). At 120 hpf, the morphology of swim bladder indicated deflation in treatments at 0.25 µM and higher. In addition, the mRNA levels of anxa5, prlra, prlrb, atp1b2 and slc12a10 were all significantly changed at 120 hpf. Taken together, we suppose that embryonic exposure to PBB inhibited the inflation of swim bladder in zebrafish probably via prlra mediated pathways. The observed changes of thyroid and adrenocortical parameters might be indirect effects evoked by PBB exposure. Overall, our results provide important data and indications for future toxicological study and risk assessment of the emerging flame retardants PBB.

Hormonal contraception in Chinese men: variations in suppression of spermatogenesis with injectable testosterone undecanoate and levonorgestrel implants.

AIM: To explore the causes of the difference in spermatogenic suppression between responders and non-responders in Chinese men treated with levonorgestrel (LNG) implants plus testosterone undecanoate (TU) injectable. METHODS: The 16 Chinese volunteers treated were divided into two groups in regard to the sperm count during the treatment period, 7 men in the responder group (Group R), including 6 azoospermia and one severe oligozoospermia, and the remaining 9 in the non-responder group (Group N), including 4 oligozoospermia and 5 with sperm counts greater than 20 x 10(6)/mL. The differences in serum profiles of FSH, LH, T, LNG and T/LH ratio were compared between the two groups and the correlation between the seminal fluid parameters and serum reproductive hormones was analyzed. RESULTS: The serum FSH level was lower in Group R than that in Group N (P<0.05), while the serum LH and LNG levels were higher in Group R than those in Group N (P<0.05). The sperm density (P<0.01, r=0.235), motility(P<0.01, r=0.326) and vitality (P<0.01, r=0.219) showed significantly positive correlation with the serum FSH level. CONCLUSION: The blood LNG and T levels, the degree of FSH inhibition and/or the sensitivity of the pituitary-testis axis to exogenous steroids, as well as the individual spermatogenetic potential and the functional status of the Leydig cells may be factors bringing about individual differences in spermatogenic suppression in Chinese men treated with LNG and TU.