Pig blastocyst-like structure models from embryonic stem cells.

Pluripotent stem cells have the potential to generate embryo models that can recapitulate developmental processes in vitro. Large animals such as pigs may also benefit from stem-cell-based embryo models for improving breeding. Here, we report the generation of blastoids from porcine embryonic stem cells (pESCs). We first develop a culture medium 4FIXY to derive pESCs. We develop a 3D two-step differentiation strategy to generate porcine blastoids from the pESCs. The resulting blastoids exhibit similar morphology, size, cell lineage composition, and single-cell transcriptome characteristics to blastocysts. These porcine blastoids survive and expand for more than two weeks in vitro under two different culture conditions. Large animal blastoids such as those derived from pESCs may enable in vitro modeling of early embryogenesis and improve livestock species' breeding practices.

Self-compression of laser pulses induced by asymmetric self-phase modulation aided by backward Raman scattering in periodic density-modulated plasma.

Here a mechanism for self-compression of laser pulses is presented, based on period density-modulated plasma. In this setup, two pump beams intersect at a small angle within the plasma. This interaction is facilitated by the ponderomotive ion mechanism, which causes a modulation in the density of plasma with long wavelengths and low amplitude. This modulation enhances the backward Raman scattering of the probe pulse. The trailing edge of the probe experiences greater energy loss, resulting in a steeper intensity gradient. This, in turn, induces an asymmetric self-phase modulation, which elevates the instantaneous frequency. It is notable that the laser in plasma exhibits opposite group velocity dispersion compared to traditional solid-state media. This unique property allows laser pulses to undergo dispersion compensation while broadening the spectrum, ultimately leading to self-compression. The 2D-PIC simulations demonstrate these phenomena, highlighting how period density-modulated plasma contributes to an asymmetric spectral distribution. The intricate interplay among self-phase modulation, group velocity, and backward Raman scattering results in the self-compressing of the laser pulse. Specifically, the pulses are compressed from their Fourier transform limit duration of 50 fs to a significantly reduced duration of 8 fs at plasma densities below 1/4 critical density, without the transverse self-focusing effects.

Triptonide protects retinal cells from oxidative damage via activation of Nrf2 signaling.

Age­related macular degeneration (AMD) is an ocular disease that threatens the visual function of older adults worldwide. Key pathological processes involved in AMD include oxidative stress, inflammation and choroidal vascular dysfunction. Retinal pigment epithelial cells and Müller cells are most susceptible to oxidative stress. Traditional herbal medicines are increasingly being investigated in the field of personalized medicine in ophthalmology. Triptonide (Tn) is a diterpene tricyclic oxide, the main active ingredient in the extract from the Chinese herbal medicinal plant Tripterygium wilfordii, and is considered an effective immunosuppressant and anti­inflammatory drug. The present study investigated the potential beneficial role of Tn in retinal oxidative damage in order to achieve personalized treatment for early AMD. An oxidative stress model of retinal cells induced by H2O2 and a retinal injury model of mice induced by light and N­Methyl­D­aspartic acid were constructed. In vitro, JC­1 staining, flow cytometry and apoptosis assay confirmed that low concentrations of Tn effectively protected retinal cells from oxidative damage, and reverse transcription­quantitative PCR and western blotting analyses revealed that Tn reduced the expression of retinal oxidative stress­related genes and inflammatory factors, which may depend on the PI3K/AKT/mTOR­induced Nrf2 signaling pathway. In vivo, by retinal immunohistochemistry, hematoxylin and eosin staining and electroretinogram assay, it was found that retinal function and structure improved and choroidal neovascularization was significantly inhibited after Tn pretreatment. These results suggested that Tn is an efficient Nrf2 activator, which can be expected to become a new intervention for diseases such as AMD, to inhibit retinal oxidative stress damage and pathological neovascularization.

Causality of genetically determined metabolites on susceptibility to prevalent urological cancers: a two-sample Mendelian randomization study and meta-analysis.

Background: Prevalent urological cancers, including kidney, prostate, bladder, and testicular cancers, contribute significantly to global cancer incidence and mortality. Metabolomics, focusing on small-molecule intermediates, has emerged as a tool to understand cancer etiology. Given the knowledge gap in this field, we employ a two-sample Mendelian randomization (MR) analysis to investigate the causal relationships between genetically determined metabolites (GDMs) and the susceptibility to four common urological cancers. Methods: The study employs genome-wide association studies (GWAS) data from European populations, featuring the most extensive case count available for both blood metabolites and four prevalent urological cancers. Preliminary and secondary MR analyses were separately conducted, employing inverse variance weighted (IVW) as the primary method. Multiple statistical analyses, including the MR-Steiger test, Cochran's Q test, leave-one-out analysis, MR-Egger intercept analysis, and MR-PRESSO analysis, were executed to ensure robustness. Additionally, a meta-analysis was carried out to consolidate findings. The weighted median (WM) method was utilized for a relatively lenient correction (PWM < 0.05). Results: After rigorous genetic variation filtering, 645 out of 1,400 metabolites were included in both preliminary and secondary MR analyses. Preliminary MR analysis identified 96 potential causal associations between 94 distinct metabolites and four urological cancers. Secondary analysis based on Finnish outcome data revealed 93 potential causal associations. Cross-database meta-analysis identified 68 blood metabolites associated with four urological cancers. Notably, 31 metabolites remained significant after using WM for correction, with additional 37 suggestive causal relationships. Reverse MR analysis revealed a significant causal association between genetically predicted prostate cancer and elevated 4-hydroxychlorothalonil levels (IVW, combined OR: 1.039, 95% CI 1.014-1.064, p = 0.002; WM, combined OR: 1.052, 95% CI 1.010-1.095, p = 0.014). Conclusion: This comprehensive MR study provides insights into the causal relationships between blood metabolites and urological cancers, revealing potential biomarkers and therapeutic targets, thereby addressing gaps in understanding and laying the foundation for targeted interventions in urological cancer research and treatment.

Immunomodulatory molecules in colorectal cancer liver metastasis.

Colorectal cancer (CRC) ranks as the third most common cancer and the second leading cause of cancer-related deaths. According to clinical diagnosis and treatment, liver metastasis occurs in approximately 50 % of CRC patients, indicating a poor prognosis. The unique immune tolerance of the liver fosters an immunosuppressive tumor microenvironment (TME). In the context of tumors, numerous membrane and secreted proteins have been linked to tumor immune evasion as immunomodulatory molecules, but much remains unknown about how these proteins contribute to immune evasion in colorectal cancer liver metastasis (CRLM). This article reviews recently discovered membrane and secreted proteins with roles as both immunostimulatory and immunosuppressive molecules within the TME that influence immune evasion in CRC primary and metastatic lesions, particularly their mechanisms in promoting CRLM. This article also addresses screening strategies for identifying proteins involved in immune evasion in CRLM and provides insights into potential protein targets for treating CRLM.

Engineering the Mechanical Stability of a Therapeutic Affibody/PD-L1 Complex by Anchor Point Selection.

Protein-protein complexes can vary in mechanical stability depending on the direction from which force is applied. Here we investigated the anisotropic mechanical stability of a molecular complex between a therapeutic non-immunoglobulin scaffold called Affibody and the extracellular domain of the immune checkpoint protein PD-L1. We used a combination of single-molecule AFM force spectroscopy (AFM-SMFS) with bioorthogonal clickable peptide handles, shear stress bead adhesion assays, molecular modeling, and steered molecular dynamics (SMD) simulations to understand the pulling point dependency of mechanostability of the Affibody:(PD-L1) complex. We observed diverse mechanical responses depending on the anchor point. For example, pulling from residue #22 on Affibody generated an intermediate unfolding event attributed to partial unfolding of PD-L1, while pulling from Affibody's N-terminus generated force-activated catch bond behavior. We found that pulling from residue #22 or #47 on Affibody generated the highest rupture forces, with the complex breaking at up to ~ 190 pN under loading rates of ~104-105 pN/sec, representing a ~4-fold increase in mechanostability as compared with low force N-terminal pulling. SMD simulations provided consistent tendencies in rupture forces, and through visualization of force propagation networks provided mechanistic insights. These results demonstrate how mechanostability of therapeutic protein-protein interfaces can be controlled by informed selection of anchor points within molecules, with implications for optimal bioconjugation strategies in drug delivery vehicles.

Physical frailty, genetic predisposition, and incident arrhythmias.

BACKGROUND: Cross-sectional evidence suggests a possible link between frailty and atrial fibrillation (AF). It remains unclear whether frailty and incident arrhythmias are longitudinally associated. This study aimed to determine whether the frailty phenotype is longitudinally associated with incident arrhythmias, especially AF. METHODS: In this prospective cohort of UK Biobank, individuals with arrhythmias at baseline, those without data for frailty phenotype, and no genetic data were excluded. Five domains of physical frailty, including weight loss, exhaustion, low physical activity, low grip strength, and slow gait speed, were assessed. A total of 142 single-nucleotide polymorphisms was used to calculate the polygenic risk score (PRS) for AF. Hospital inpatient records and death records were used to identify incident arrhythmias. RESULTS: This study included 464 154 middle-aged and older adults (mean age 56.4 ± 8.1 years, 54.7% female) without arrhythmia at baseline. During a median follow-up of 13.4 years (over 5.9 million person-years), 46 454 new-onset arrhythmias cases were recorded. In comparison with non-frailty, the multivariable-adjusted hazard ratios (HRs) of AF were 1.12 (95% CI: 1.09, 1.15, P < 0.0001) and 1.44 (95% CI: 1.36, 1.51, P < 0.0001) for participants with pre-frailty and frailty, respectively. Similar associations were observed for other arrhythmias. We found that slow gait speed presented the strongest risk factor in predicting all arrhythmias, including AF (HR 1.34, 95% CI: 1.30, 1.39), bradyarrhythmias (HR 1.30, 95% CI: 1.22, 1.37), conduction system diseases (HR 1.29, 95% CI: 1.22, 1.36), supraventricular arrhythmias (HR 1.32, 95% CI: 1.19, 1.47), and ventricular arrhythmias (HR 1.37, 95% CI: 1.25, 1.51), with all P values <0.0001. In addition to slow gait speed, weight loss (HR 1.13, 95% CI: 1.09, 1.16, P < 0.0001) and exhaustion (HR 1.11, 95% CI: 1.07, 1.14, P < 0.0001) were significantly associated with incident AF, whereas insignificant associations were observed for physical activity (HR 1.03, 95% CI: 0.996, 1.08, P = 0.099) and low grip strength (HR 1.00, 95% CI: 0.97, 1.03, P = 0.89). We observed a significant interaction between genetic predisposition and frailty on incident AF (P for interaction <0.0001), where those with frailty and the highest tertile of PRS had the highest risk of AF (HR 3.34, 95% CI: 3.08, 3.61, P < 0.0001) compared with those with non-frailty and the lowest tertile of PRS. CONCLUSIONS: Physical pre-frailty and frailty were significantly and independently associated with incident arrhythmias. Although direct causal inference still needs to be further validated, these results suggested the importance of assessing and managing frailty for arrhythmia prevention.

Totally Caged Type I Pro-Photosensitizer for Oxygen-Independent Synergistic Phototherapy of Hypoxic Tumors.

Activatable type I photosensitizers are an effective way to overcome the insufficiency and imprecision of photodynamic therapy in the treatment of hypoxic tumors, however, the incompletely inhibited photoactivity of pro-photosensitizer and the limited oxidative phototoxicity of post-photosensitizer are major limitations. It is still a great challenge to address these issues using a single and facile design. Herein, a series of totally caged type I pro-photosensitizers (Pro-I-PSs) are rationally developed that are only activated in tumor hypoxic environment and combine two oxygen-independent therapeutic mechanisms under single-pulse laser irradiation to enhance the phototherapeutic efficacy. Specifically, five benzophenothiazine-based dyes modified with different nitroaromatic groups, BPN 1-5, are designed and explored as latent hypoxia-activatable Pro-I-PSs. By comparing their optical responses to nitroreductase (NTR), it is identified that the 2-methoxy-4-nitrophenyl decorated dye (BPN 2) is the optimal Pro-I-PSs, which can achieve NTR-activated background-free fluorescence/photoacoustic dual-modality tumor imaging. Furthermore, upon activation, BPN 2 can simultaneously produce an oxygen-independent photoacoustic cavitation effect and a photodynamic type I process at single-pulse laser irradiation. Detailed studies in vitro and in vivo indicated that BPN 2 can effectively induce cancer cell apoptosis through synergistic effects. This study provides promising potential for overcoming the pitfalls of hypoxic-tumor photodynamic therapy.

Research on Medical Image Segmentation Method Based on Improved U-Net3.

Computer assisted diagnostic technology has been widely used in clinical practice, specifically focusing on medical image segmentation. Its purpose is to segment targets with certain special meanings in medical images and extract relevant features, providing reliable basis for subsequent clinical diagnosis and research. However, because of different shapes and complex structures of segmentation targets in different medical images, some imaging techniques have similar characteristics, such as intensity, color, or texture, for imaging different organs and tissues. The localization and segmentation of targets in medical images remains an urgent technical challenge to be solved. As such, an improved full scale skip connection network structure for the CT liver image segmentation task is proposed. This structure includes a biomimetic attention module between the shallow encoder and the deep decoder, and the feature fusion proportion coefficient between the two is learned to enhance the attention of the overall network to the segmented target area. In addition, based on the traditional point sampling mechanism, an improved point sampling strategy is proposed for characterizing medical images to further enhance the edge segmentation effect of CT liver targets. The experimental results on the commonly used combined (CT-MR) health absolute organ segmentation (CHAOS) dataset show that the average dice similarity coefficient (DSC) can reach 0.9467, the average intersection over union (IOU) can reach 0.9623, and the average F1 score can reach 0.9351. This indicates that the model can effectively learn image detail features and global structural features, leading to improved segmentation of liver images.

Effects and underlying mechanism of micro-nano-structured zirconia surfaces on biological behaviors of human gingival fibroblasts under inflammatory conditions.

Zirconia is one of the most commonly used materials for abutments of dental implants, especially in the anterior region. Soft tissue integration to the zirconia abutment surface remains a challenge. Peri-implant soft tissue integration serves as a physiological barrier, attenuating pathogen penetration and preventing peri­implant disease. The surface microstructure of zirconia has significant effects on the biological behaviors of human gingival fibroblasts (HGFs), but the effects under inflammatory conditions are still unclear. In this study, we established two micro-nano structures on zirconia surfaces using a femtosecond laser, including microgrooves with widths of 30 µm (G3) and 60 µm (G6) and depths of 5 µm, and nanoparticles inside the microgrooves. Polished surfaces were used as controls. HGFs were seeded onto the three groups of zirconia specimens and stimulated with lipopolysaccharide. The HGFs on micro-nano-structured zirconia surfaces exhibited lower inflammatory responses and higher cell adhesion, proliferation, and migration under inflammatory conditions compared with the polished surfaces. Additionally, the G3 group exhibited lower inflammatory responses and higher cell adhesion and migration than the G6 group. The micro-nano-structured zirconia surface exhibited decreased neutrophil infiltration and increased M2-type macrophage polarization in vivo. To explore the molecular mechanism, RNA sequencing and gene silencing were utilized, which revealed two critical target genes regulated by the G3 group. Overall, we proposed an innovative micro-nano-structured zirconia surface that reduced the in vitro and in vivo inflammatory responses and promoted HGF adhesion, migration, and proliferation under inflammatory conditions, in which TRAFD1 and NLRC5 were the underlying key genes. STATEMENT OF SIGNIFICANCE: Zirconia is one of the most commonly used materials for abutments, especially in the anterior region. The surface microstructure of zirconia has significant effects on the biological behaviors of human gingival fibroblasts (HGFs), but few studies have investigated these effects under inflammatory conditions, and the mechanism remains unclear. In this study, we developed an innovative micro-nano-structured zirconia surface using a femtosecond laser, which reduces the in vitro and in vivo pro-inflammatory responses and promotes HGFs adhesion, migration, and proliferation under inflammatory conditions compared with the polished zirconia surface. The potential underlying mechanism was also investigated. This work has provided some theoretical basis for the micro-nano-structured zirconia surface in potentially reducing the inflammation and enhancing peri­implant soft-tissue integration under inflammatory conditions.

Effects of high moisture ear corn on production performance, milk fatty acid composition, serum antioxidant status, and immunity in primiparous dairy cows.

OBJECTIVE: This study evaluated the effects of high moisture ear corn (HMEC) on production performance, milk fatty acid composition, serum antioxidant status, and immunity in primiparous dairy cows. METHODS: A total of 45 healthy primiparous Holstein cows (36.50±4.30 kg of milk/d, 201±9.00 lactating days in milk) were sorted into 3 groups: control group (CG, n = 15); 50% HMEC (replacing 50% steam-flaked corn with HMEC, n = 15); and 100% HMEC (replacing steam-flaked corn with HMEC, n = 15) on an equal dry matter (DM) basis. The study consisted of adaptation period of 14 days, followed by a formal period of 60 days. Feed intake and milk yield were recorded daily. Milk and blood samples were collected on 1, 30, and 60 d of the experimental period. RESULTS: The 50% HMEC group and 100% HMEC group significantly increased (p<0.05) milk yield and DM intake in dairy cows compared to the control group (CG). The 100% HMEC group showed an increase (p<0.05) in 4% fat-corrected milk (4% FCM). Both the 50% HMEC group and 100% HMEC group exhibited significant decreases (p<0.05) in the content of C10:0, C12:0, and C14:0 fatty acids, along with a significant increase (p<0.05) in cis-9C18:1 content. The saturated fatty acid content was significantly lower (p<0.05) in the 50% HMEC and 100% HMEC groups than that of CG. Conversely, the monounsaturated fatty acid content was higher (p<0.05) in the 50% HMEC and 100% HMEC groups than that in CG. Notably, the 100% HMEC group significantly increased (p<0.05) the serum superoxide dismutase and glutathione peroxidase content, while also decreasing the serum malondialdehyde content (p<0.05). Moreover, the 100% HMEC group significantly increased (p<0.05) the content of immunoglobulin G (IgG) and IgM. CONCLUSION: High moisture ear corn could improve production performance and milk fatty acid levels and enhance immunity and antioxidant capacity in dairy cows. These results lay the foundation for the wider application of HMEC in ruminant animal diets.

Effects of four antibiotics on the photosynthetic light reactions in the green alga Chlorella pyrenoidosa.

Antibiotics are ubiquitously present in aquatic environments, posing a serious ecological risk to aquatic ecosystems. However, the effects of antibiotics on the photosynthetic light reactions of freshwater algae and the underlying mechanisms are relatively less understood. In this study, the effects of 4 representative antibiotics (clarithromycin, enrofloxacin, tetracycline, and sulfamethazine) on a freshwater alga (Chlorella pyrenoidosa) and the associated mechanisms, primarily focusing on key regulators of the photosynthetic light reactions, were evaluated. Algae were exposed to different concentrations of clarithromycin (0.0-0.3 mg/L), enrofloxacin (0.0-30.0 mg/L), tetracycline (0.0-10.0 mg/L), and sulfamethazine (0.0-50.0 mg/L) for 7 days. The results showed that the 4 antibiotics inhibited the growth, the photosynthetic pigment contents, and the activity of antioxidant enzymes. In addition, exposure to clarithromycin caused a 118.4 % increase in malondialdehyde (MDA) levels at 0.3 mg/L. Furthermore, the transcripts of genes for the adenosine triphosphate (ATP) - dependent chloroplast proteases (ftsH and clpP), genes in photosystem II (psbA, psbB, and psbC), genes related to ATP synthase (atpA, atpB, and atpH), and petA (related to cytochrome b6/f complex) were altered by clarithromycin. This study contributes to a better understanding of the risk of antibiotics on primary producers in aquatic environment.

An AND-Gate Photoacoustic Probe for Cys and H2S Precise Photoacoustic Sensing in Localized Tumors.

Photoacoustic (PA) tomography has shown many promising aspects in noninvasive and precise imaging of deep-localized biomarkers. However, these traditional single-locked PA probes always face challenges in precise PA imaging with high specificity. Here, we report a novel AND-gate photoacoustic probe, BAE, to improve tumor imaging accuracy via the combination of two tumor-associated biomarkers, cysteine (Cys) and hydrogen sulfide (H2S). Only when Cys and H2S are concurrently introduced into the detection system does the absorption of BAE red-shift from the initial 680 to 810 nm, thereby showing a 5.29-fold enhancement in its PA signal at 810 nm. The good specificity of BAE is proven, since an obvious PA signal could be observed only in the solution containing both Cys and H2S and was not affected by other reactive sulfur species. After being taken up by tumors with the assistance of a nanomicelle, the AND-gate PA probe BAE was applied for dynamic real-time monitoring of Cys and H2S in vivo, achieving precise identification of tumors. This AND-gate PA probe provides a potential technical tool for precise sensing analysis of deep-seated diseases.

Ultrathin Al2O3film modification on waterborne epoxy coatings by atomic layer deposition for augmenting the corrosion resistance.

The polar channels formed by the curing of waterborne anticorrosive coatings compromise their water resistance, leading to coating degradation and metal corrosion. To enhance the anticorrosive performance of waterborne coatings, this study proposed a novel method of depositing ultrathin Al2O3films on the surface of waterborne epoxy coatings by atomic layer deposition, a technique that can modify the surface properties of polymer materials by depositing functional films. The Al2O3-modified coatings exhibited improved sealing and barrier properties by closing the polar channels and surface defects and cracks. The surface structure and morphology of the modified coatings were characterized by x-ray photoelectron spectroscopy and scanning electron microscopy. The hydrophilicity and corrosion resistance of the modified coatings were evaluated by water contact angle measurement, Tafel polarization curve, and electrochemical impedance spectroscopy. The results indicated that the water contact angle of the Al2O3-modified coating increased by 48° compared to the unmodified coating, and the protection efficiency of the modified coating reached 99.81%. The Al2O3-modified coating demonstrated high anticorrosive efficiency and potential applications for metal anticorrosion in harsh marine environments.

The effect of obesity on the outcome of thoracic endovascular aortic repair: a systematic review and meta-analysis.

Background: Obesity is a well-known predictor for poor postoperative outcomes of vascular surgery. However, the association between obesity and outcomes of thoracic endovascular aortic repair (TEVAR) is still unclear. This systematic review and meta-analysis was performed to assess the roles of obesity in the outcomes of TEVAR. Methods: We systematically searched the Web of Science and PubMed databases to obtain articles regarding obesity and TEVAR that were published before July 2023. The odds ratio (OR) or hazard ratio (HR) was used to assess the effect of obesity on TEVAR outcomes. Body mass index (BMI) was also compared between patients experiencing adverse events after TEVAR and those not experiencing adverse events. The Newcastle-Ottawa Scale was used to evaluate the quality of the enrolled studies. Results: A total of 7,849 patients from 10 studies were included. All enrolled studies were high-quality. Overall, the risk of overall mortality (OR = 1.49, 95% CI [1.02-2.17], p = 0.04) was increased in obese patients receiving TEVAR. However, the associations between obesity and overall complications (OR = 2.41, 95% CI [0.84-6.93], p = 0.10) and specific complications were all insignificant, including stroke (OR = 1.39, 95% CI [0.56-3.45], p = 0.48), spinal ischemia (OR = 0.97, 95% CI [0.64-1.47], p = 0.89), neurological complications (OR = 0.13, 95% CI [0.01-2.37], p = 0.17), endoleaks (OR = 1.02, 95% CI [0.46-2.29], p = 0.96), wound complications (OR = 0.91, 95% CI [0.28-2.96], p = 0.88), and renal failure (OR = 2.98, 95% CI [0.92-9.69], p = 0.07). In addition, the patients who suffered from postoperative overall complications (p < 0.001) and acute kidney injury (p = 0.006) were found to have a higher BMI. In conclusion, obesity is closely associated with higher risk of mortality after TEVAR. However, TEVAR may still be suitable for obese patients. Physicians should pay more attention to the perioperative management of obese patients.

Heparin-free veno-arterial extracorporeal membrane oxygenation in lung transplantation: a retrospective cohort study.

BACKGROUND: In lung transplantation (LTx) surgery, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide mechanical circulatory support to patients with cardiopulmonary failure. However, the use of heparin in the administration of ECMO can increase blood loss during LTx. This study aimed to evaluate the safety of heparin-free V-A ECMO strategies. METHODS: From September 2019 to April 2022, patients who underwent lung transplantation at the First Affiliated Hospital of Guangzhou Medical University were retrospectively reviewed. A total of 229 patients were included, including 117 patients in the ECMO group and 112 in the non-ECMO group. RESULT: There was no significant difference in the incidence of thrombus events and bleeding requiring reoperation between the two groups. The in-hospital survival rate after single lung transplantation (SLTx) was 81.08%in the ECMO group and 85.14% in the Non-ECMO group, (P = 0.585). The in-hospital survival rate after double lung transplantation (DLTx) was 80.00% in the ECMO group and 92.11% in the Non-ECMO groups (P = 0.095). CONCLUSIONS: In conclusion, the findings of this study suggest that the heparin-free V-A ECMO strategy in lung transplantation is a safe approach that does not increase the incidence of perioperative thrombotic events or bleeding requiring reoperation.

Reconstruction the feedback regulation of amino acid metabolism to develop a non-auxotrophic L-threonine producing Corynebacterium glutamicum.

L-Threonine is an important feed additive with the third largest market size among the amino acids produced by microbial fermentation. The GRAS (generally regarded as safe) industrial workhorse Corynebacterium glutamicum is an attractive chassis for L-threonine production. However, the present L-threonine production in C. glutamicum cannot meet the requirement of industrialization due to the relatively low production level of L-threonine and the accumulation of large amounts of by-products (such as L-lysine, L-isoleucine, and glycine). Herein, to enhance the L-threonine biosynthesis in C. glutamicum, releasing the aspartate kinase (LysC) and homoserine dehydrogenase (Hom) from feedback inhibition by L-lysine and L-threonine, respectively, and overexpressing four flux-control genes were performed. Next, to reduce the formation of by-products L-lysine and L-isoleucine without the cause of an auxotrophic phenotype, the feedback regulation of dihydrodipicolinate synthase (DapA) and threonine dehydratase (IlvA) was strengthened by replacing the native enzymes with heterologous analogues with more sensitive feedback inhibition by L-lysine and L-isoleucine, respectively. The resulting strain maintained the capability of synthesizing enough amounts of L-lysine and L-isoleucine for cell biomass formation but exhibited almost no extracellular accumulation of these two amino acids. To further enhance L-threonine production and reduce the by-product glycine, L-threonine exporter and homoserine kinase were overexpressed. Finally, the rationally engineered non-auxotrophic strain ZcglT9 produced 67.63 g/L (17.2% higher) L-threonine with a productivity of 1.20 g/L/h (108.0% higher) in fed-batch fermentation, along with significantly reduced by-product accumulation, representing the record for L-threonine production in C. glutamicum. In this study, we developed a strategy of reconstructing the feedback regulation of amino acid metabolism and successfully applied this strategy to de novo construct a non-auxotrophic L-threonine producing C. glutamicum. The main end by-products including L-lysine, L-isoleucine, and glycine were almost eliminated in fed-batch fermentation of the engineered C. glutamicum strain. This strategy can also be used for engineering producing strains for other amino acids and derivatives.

Stock Assessment of the Commercial Small Pelagic Fishes in the Beibu Gulf, the South China Sea, 2006-2020.

Long-term variations in population structure, growth, mortality, exploitation rate, and recruitment pattern of two major commercial small pelagic fishes (CSPFs) (Decapterus maruadsi and Trachurus japonicus) are reported based on bottom trawl survey data collected during 2006-2020 in the Beibu Gulf, South China Sea. All individuals collected during each sampling quarter over a period of 15 years were subjected to laboratory-based analysis. In this study, the stock of D. maruadsi and T. japonicus inhabiting the Beibu Gulf was assessed using length-based methods (bootstrapped electronic length frequency analysis (ELEFAN)) to complete stock assessment in different fishery management periods (the division of fisheries management periods was based on China's input and output in the South China Sea offshore fisheries over 15 years, specifically divided into period I (2006-2010), period II (2011-2015), and period III (2016-2020)). The results showed that the mean body length, dominant body size, and estimated asymptotic length of two CSPFs decreased, whereas their growth coefficient decreased, indicating miniaturization and slower growth, respectively. Estimated exploitation rates and catching body length for two CSPFs indicated that both stocks in the Beibu Gulf were overexploited in period I and moderately exploited after 2011. These stocks were taking a good turn in status in period III, with the exploitation rate much lower than the initial period and reversing the downward trend in catching body length. Furthermore, the variations in the spawning season of the two CSPF stocks and their barely satisfactory expected yield indicated the complexity of the current fishery management in the Beibu Gulf. These results suggest that management measures to reduce fishing pressure may have a positive influence on the biological characteristics of those CSPFs in the Beibu Gulf; however, the stock structure already affected by overfishing will be a huge challenge for the conservation and restoration of fisheries resources in the future. Given that the current stocks of D. maruadsi and T. japonicus in the Beibu Gulf still have low first-capture body length (Lc) and high fishing mortality (F) (compared to F0.1), we identify a need to refine population structure by controlling fishing efforts and increasing catchable size, and more consideration should be given to the local fishery resource status in fisheries management.

Single Side-Chain-Modulatory of Hemicyanine for Optimized Fluorescence and Photoacoustic Dual-Modality Imaging of H2S In Vivo.

Near-infrared fluorescence (NIRF)/photoacoustic (PA) dual-modality imaging integrated high-sensitivity fluorescence imaging with deep-penetration PA imaging has been recognized as a reliable tool for disease detection and diagnosis. However, it remains an immense challenge for a molecule probe to achieve the optimal NIRF and PA imaging by adjusting the energy allocation between radiative transition and nonradiative transition. Herein, a simple but effective strategy is reported to engineer a NIRF/PA dual-modality probe (Cl-HDN3) based on the near-infrared hemicyanine scaffold to optimize the energy allocation between radiative and nonradiative transition. Upon activation by H2S, the Cl-HDN3 shows a 3.6-fold enhancement in the PA signal and a 4.3-fold enhancement in the fluorescence signal. To achieve the sensitive and selective detection of H2S in vivo, the Cl-HDN3 is encapsulated within an amphiphilic lipid (DSPE-PEG2000) to form the Cl-HDN3-LP, which can successfully map the changes of H2S in a tumor-bearing mouse model with the NIRF/PA dual-modality imaging. This work presents a promising strategy for optimizing fluorescence and PA effects in a molecule probe, which may be extended to the NIRF/PA dual-modality imaging of other disease-relevant biomarkers.