Enhancing precision in effective regurgitant orifice area estimation by transthoracic echocardiography for functional mitral regurgitation using computational fluid dynamics.

Computational fluid dynamics (CFD) was used to identify factors influencing the accuracy of the hemispherical proximal isovelocity surface area (PISA) method in calculating the effective regurgitant orifice area (EROA) for patients with functional mitral regurgitation (FMR). Ninety-nine CFD models were constructed to investigate the impact of regurgitant orifice shape and leaflet tethering on the EROA calculation using the PISA method. The correction factors for regurgitation orifice shape (CFs) and for leaflet tethering (CFt) were derived by comparing the 2D PISA method and the actual orifice area. The correction formula was then tested in vivo via 2D transthoracic echocardiography with 3D transesophageal echocardiography of the vena contracta area (VCA) as a reference method in 62 patients with FMR. Based on the CFD simulation results, the two major factors for correcting the EROA calculation were vena contracta length (VCL) and coaptation depth (CD). The correction formula for the EROA was corrected effective regurgitant orifice area (CEROA) = EROA*CFs*CFt, where CFs = 0.59 × VCL(cm) + 0.6 × MR Vmax(cm/s)-0.63 × PISA R(cm)-1.51 and CFt = 0.4 × CD (cm) + 0.96. The correction formula was applied to FMR patients, and the bias and LOA between the CEROA and VCA (0.01 ± 0.13 cm2) were much smaller than those between the EROA and VCA (0.26 ± 0.32 cm2). The CFD-based correction formula improves the accuracy of the EROA calculation based on the hemispheric PISA method, possibly leading to more accurate and reliable data for treatment decision-making in FMR patients.

Sequential severe immune-related adverse events induced by PD-1 inhibitor: a case report and literature review.

In a variety of cancers, immune checkpoint inhibitors (ICIs) have demonstrated substantial survival advantages. Nevertheless, the widespread use of ICIs in the clinic has resulted in a growing interest in immune-related adverse events (irAEs) and their treatment methods. This paper reports a case in which a patient with three sequential severe irAEs was successfully treated. After undergoing two regimens of sintilimab in conjunction with chemotherapy for advanced lung cancer, the patient developed myocarditis combined with hepatitis. Subsequently, the patient developed pneumonia following remission from treatment. We also discuss the mechanism of irAEs, principles of treatment, and progress in the study of biomarkers for early prediction of irAEs by reviewing the literature.

ATF3 is involved in rSjP40-mediated inhibition of HSCs activation in Schistosoma japonicum-infected mice.

Schistosomiasis is a parasitic disease characterized by liver fibrosis, a process driven by the activation of hepatic stellate cells (HSCs) and subsequent collagen production. Previous studies from our laboratory have demonstrated the ability of Schistosoma japonicum protein P40 (SjP40) to inhibit HSCs activation and exert an antifibrotic effect. In this study, we aimed to elucidate the molecular mechanism underlying the inhibitory effect of recombinant SjP40 (rSjP40) on HSCs activation. Using a cell model in which rSjP40 inhibited LX-2 cell activation, we performed RNA-seq analyses and identified ATF3 as the most significantly altered gene. Further investigation revealed that rSjP40 inhibited HSCs activation partly by suppressing ATF3 activation. Knockdown of ATF3 in mouse liver significantly alleviated S. japonicum-induced liver fibrosis. Moreover, our results indicate that ATF3 is a direct target of microRNA-494-3p, a microRNA associated with anti-liver fibrosis effects. rSjP40 was found to downregulate ATF3 expression by upregulating microRNA-494-3p in LX-2 cells. This downregulation led to the inhibition of the expression of liver fibrosis proteins α-SMA and COL1A1, ultimately alleviating liver fibrosis caused by S. japonicum.

Minimizing Interfacial Energy Loss and Volatilization of Formamidinium via Polymer-Assisted D-A supramolecular Self-Assembly Interface for Inverted Perovskite Solar Cells with 25.78% Efficiency.

2D perovskite passivation strategies effectively reduce defect-assisted carrier nonradiative recombination losses on the perovskite surface. Nonetheless, severe energy losses are causing by carrier thermalization, interfacial nonradiative recombination, and conduction band offset still persist at heterojunction perovskite/PCBM interfaces, which limits further performance enhancement of inverted heterojunction PSCs. Here, 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (5FTPP) is introduced between 3D/2D perovskite heterojunction and PCBM. Compared to tetraphenylporphyrin without electron-withdrawing fluoro-substituents, 5FTPP can self-assemble with PCBM at interface into donor-acceptor (D-A) complex with stronger supramolecular interaction and lower energy transfer losses. This rapid energy transfer from donor (5FTPP) to acceptor (PCBM) within femtosecond scale is demonstrated to enlarge hot carrier extraction rates and ranges, reducing thermalization losses. Furthermore, the incorporation of polystyrene derivative (PD) reinforces D-A interaction by inhibiting self-π-π stacking of 5FTPP, while fine-tuning conduction band offset and suppressing interfacial nonradiative recombination via Schottky barrier, dipole, and n-doping. Notably, the multidentate anchoring of PD-5FTPP with FA+, Pb2+, and I- mitigates the adverse effects of FA+ volatilization during thermal stress. Ultimately, devices with PD-5FTPP achieve a power conversion efficiency of 25.78% (certified: 25.36%), maintaining over 90% of initial efficiency after 1000 h of continuous illumination at the maximum power point (65 °C) under ISOS-L-2 protocol.

Hydrogel-Based Treatment of House Dust Mite-Induced Atopic Dermatitis through Triple Cleaning of Mites, Bacteria, and ROS-Related Inflammation.

Atopic dermatitis (AD) is a chronic and recurrent inflammatory disease caused by abnormalities in skin immunoregulation. House dust mite can directly damage the skin barrier and thus sensitize the skin, which is one of the main allergens inducing AD in humans and widely exists in daily life. Meanwhile, the accompanying bacterial infections and exposure to additional allergens exacerbate the condition by generating excessive reactive oxygen species (ROS). Herein, we have developed the CPDP hydrogel with injectable and self-healing ability to combat pathogenic microorganisms and inflammatory environments for AD therapy. In vitro experiments have affirmed the efficacy of the CPDP hydrogel in combating mites, killing bacteria, and scavenging ROS. In a mouse model closely mimicking HDM-induced AD, the CPDP hydrogel has shown superior therapeutic effects, including reducing epidermal thickness and mast cell count, increasing collagen deposition, as well as down-regulating pro-inflammatory factors.

Relating the carbon sources to denitrifying community in full-scale wastewater treatment plants.

Carbon source is a key factor determining the denitrifying effectiveness and efficiency in wastewater treatment plants (WWTPs). Whereas, the relationships between diverse and distinct denitrifying communities and their favorable carbon sources in full-scale WWTPs were not well-understood. This study performed a systematic analysis of the relationships between the denitrifying community and carbon sources by using 15 organic compounds from four categories and activated sludge from 8 full-scale WWTPs. Results showed that, diverse denitrifying bacteria were detected with distinct relative abundances in 8 WWTPs, such as Haliangium (1.98-4.08%), Dechloromonas (2.00-3.01%), Thauera (0.16-1.06%), Zoogloea (0.09-0.43%), and Rhodoferax (0.002-0.104%). Overall, acetate resulted in the highest denitrifying activities (1.21-4.62 mg/L/h/gMLSS), followed by other organic acids (propionate, butyrate and lactate, etc.). Detectable dissimilatory nitrate reduction to ammonium (DNRA) was observed for all 15 carbon sources. Methanol and glycerol resulted in the highest DRNA. Acetate, butyrate, and lactate resulted in the lowest DNRA. Redundancy analysis and 16S cDNA amplicon sequencing suggested that carbon sources within the same category tended to correlate to similar denitrifiers. Methanol and ethanol were primarily correlated to Haliangium. Glycerol and amino acids (glutamate and aspartate) were correlated to Inhella and Sphaerotilus. Acetate, propionate, and butyrate were positively correlated to a wide range of denitrifiers, explaining the high efficiency of these carbon sources. Additionally, even within the same genus, different amplicon sequence variants (ASVs) performed distinctly in terms of carbon source preference and denitrifying capabilities. These findings are expected to benefit carbon source formulation and selection in WWTPs.

The role of microRNA-142a in Toxoplasma gondii infection-induced downregulation of Foxp3: implications for adverse pregnancy outcomes.

BACKGROUND: Toxoplasma gondii (T. gondii) is capable of infecting nearly all warm-blooded animals and approximately 30% of the global population. Though most infections are subclinical in immunocompetent individuals, congenital contraction can lead to severe consequences such as spontaneous abortion, stillbirth, and a range of cranio-cerebral and/or ocular abnormalities. Previous studies reported that T. gondii-infected pregnancy mice unveiled a deficit in both the amount and suppressive functions of regulatory T (Treg) cells, accompanied with reduced levels of forkhead box p3 (Foxp3). Recently, accumulative studies have demonstrated that microRNAs (miRNAs) are, to some extent, relevant to T. gondii infection. However, the link between alterations in miRNAs and downregulation of Foxp3 triggered by T. gondii has been only sporadically studied. METHODS: Quantitative reverse transcription polymerase chain reaction (RT-qPCR), protein blotting and immunofluorescence were employed to evaluate the impact of T. gondii infection and antigens on miRNA transcription and Foxp3 expression. Dual-luciferase reporter gene assays were performed to examine the fluorescence activity in EL4 cells, which were transfected with recombinant plasmids containing full-length/truncated/mutant microRNA-142a-3p (miR-142a) promoter sequence or wild type/mutant of Foxp3 3' untranslated region (3' UTR). RESULTS: We found a pronounced increase in miR-142a transcription, concurrent with a decrease in Foxp3 expression in T. gondii-infected mouse placental tissue. Similarly, comparable findings have been experimentally confirmed through the treatment of EL4 cells with T. gondii antigens (TgAg) in vitro. Simultaneously, miR-142a mimics attenuated Foxp3 expression, whereas its inhibitors markedly augmented Foxp3 expression. miR-142a promoter activity was elevated upon the stimulation of T. gondii antigens, which mitigated co-transfection of mutant miR-142a promoter lacking P53 target sites. miR-142a mimics deceased the fluorescence activity of Foxp3 3' untranslated region (3' UTR), but it did not affect the fluorescence activity upon the co-transfection of mutant Foxp3 3' UTR lacking miR-142a target site. CONCLUSION: In both in vivo and in vitro studies, a negative correlation was discovered between Foxp3 expression and miR-142a transcription. TgAg enhanced miR-142a promoter activity to facilitate miR-142a transcription through a P53-dependent mechanism. Furthermore, miR-142a directly targeted Foxp3 3' UTR, resulting in the downregulation of Foxp3 expression. Therefore, harnessing miR-142a may be a possible therapeutic approach for adverse pregnancy caused by immune imbalances, particularly those induced by T. gondii infection.

Two new clades recovered at high temperatures provide novel phylogenetic and genomic insights into Candidatus Accumulibacter.

Candidatus Accumulibacter, a key genus of polyphosphate-accumulating organisms, plays key roles in lab- and full-scale enhanced biological phosphorus removal (EBPR) systems. A total of 10 high-quality Ca. Accumulibacter genomes were recovered from EBPR systems operated at high temperatures, providing significantly updated phylogenetic and genomic insights into the Ca. Accumulibacter lineage. Among these genomes, clade IIF members SCELSE-3, SCELSE-4, and SCELSE-6 represent the to-date known genomes encoding a complete denitrification pathway, suggesting that Ca. Accumulibacter alone could achieve complete denitrification. Clade IIC members SSA1, SCUT-1, SCELCE-2, and SCELSE-8 lack the entire set of denitrifying genes, representing to-date known non-denitrifying Ca. Accumulibacter. A pan-genomic analysis with other Ca. Accumulibacter members suggested that all Ca. Accumulibacter likely has the potential to use dicarboxylic amino acids. Ca. Accumulibacter aalborgensis AALB and Ca. Accumulibacter affinis BAT3C720 seemed to be the only two members capable of using glucose for EBPR. A heat shock protein Hsp20 encoding gene was found exclusively in genomes recovered at high temperatures, which was absent in clades IA, IC, IG, IIA, IIB, IID, IIG, and II-I members. High transcription of this gene in clade IIC members SCUT-2 and SCUT-3 suggested its role in surviving high temperatures for Ca. Accumulibacter. Ambiguous clade identity was observed for newly recovered genomes (SCELSE-9 and SCELSE-10). Five machine learning models were developed using orthogroups as input features. Prediction results suggested that they belong to a new clade (IIK). The phylogeny of Ca. Accumulibacter was re-evaluated based on the laterally derived polyphosphokinase 2 gene, showing improved resolution in differentiating different clades.

Efficient Charge Transport in Inverted Perovskite Solar Cells via 2D/3D Ferroelectric Heterojunction.

While the 2D/3D heterojunction is an effective method to improve the power conversion efficiency (PCE) of perovskite solar cells (PSCs), carriers are often confined in the quantum wells (QWs) due to the unique structure of 2D perovskite, which makes the charge transport along the out-of-plane direction difficult. Here, a 2D/3D ferroelectric heterojunction formed by 4,4-difluoropiperidine hydrochloride (2FPD) in inverted PSCs is reported. The enriched 2D perovskite (2FPD)2PbI4 layer with n = 1 on the perovskite surface exhibits ferroelectric response and has oriented dipoles along the out-of-plane direction. The ferroelectricity of the oriented dipole layer facilitates the enhancement of the built-in electric field (1.06 V) and the delay of the cooling process of hot carriers, reflected in the high carrier temperature (above 1400 K) and the prolonged photobleach recovery time (139.85 fs, measured at bandgap), improving the out-of-plane conductivity. In addition, the alignment of energy levels is optimized and exciton binding energy (32.8 meV) is reduced by changing the dielectric environment of the surface. Finally, the 2FPD-treated PSCs achieve a PCE of 24.82% (certified: 24.38%) with the synergistic effect of ferroelectricity and defect passivation, while maintaining over 90% of their initial efficiency after 1000 h of maximum power point tracking.

Optimization of α-L-arabinofuranosidase CcABF on clarification and beneficial active substances in fermented ginkgo kernel juice by artificial neural network and genetic algorithm.

This study aimed at using α-L-arabinofuranosidase CcABF to improve the clarity and active substances in fermented ginkgo kernel juice by artificial neural network (ANN) modeling and genetic algorithm (GA) optimization. A credible three-layer feedforward ANN model was established to predict the optimal parameters for CcABF clarification. The experiments proved the highest transmittance of 89.40% for fermented ginkgo kernel juice with this understanding, which exhibited a 25.56% increase over the unclarified group. With the clarification of CcABF, the antioxidant capacity in juice was enhanced with the increase of total phenolic and flavone contents, and the maximum DPPH and hydroxyl radical scavenging rates were increased by 89.71% and 26.65%, respectively. The contents of toxic ginkgolic acids declined markedly, while the active ingredients of ginkgetin and ginkgolide B showed a modest increase. Moreover, changes in free amino acids and volatile compounds improved the nutritive value and flavor of clarified fermented ginkgo kernel juice.

Inhibition of Foxp3 expression in the placenta of mice infected intraperitoneally by toxoplasma gondii tachyzoites: insights into the PPARγ/miR-7b-5p/Sp1 signaling pathway.

BACKGROUND: Toxoplasma gondii, an obligate intracellular parasitic protozoa, infects approximately 30% of the global population. Contracting T. gondii at the primary infection of the mother can result in neonatal microcephaly, chorioretinitis, hydrocephalus, or mortality. Our previous study indicated that pregnant mice infected with T. gondii displayed a decrease in both the number and the suppressive ability of regulatory T cells, accompanied by the reduced Forkhead box P3 (Foxp3). Numerous studies have proved that microRNAs (miRNAs) are implicated in T. gondii infection, but there is meager evidence on the relationship between alterations of miRNAs and downregulation of Foxp3 induced by T. gondii. METHODS: Quantitative reverse transcription polymerase chain reaction was utilized to detect the transcriptions of miRNAs and Foxp3. Protein blotting and immunofluorescence were used to detect the expressions of Foxp3 and related transcription factors. The structure of mouse placenta was observed by hematoxylin and eosin (HE) staining. To examine the activity of miR-7b promoter and whether miR-7b-5p targets Sp1 to suppress Foxp3 expression, we constructed recombinant plasmids containing the full-length/truncated/mutant miR-7b promoter sequence or wildtype/mutant of Sp1 3' untranslated region (3' UTR) to detect the fluorescence activity in EL4 cells. RESULTS: In T. gondii-infected mice, miR-7b transcription was significantly elevated, while Foxp3 expression was decreased in the placenta. In vitro, miR-7b mimics downregulated Foxp3 expression, whereas its inhibitors significantly upregulated Foxp3 expression. miR-7b promoter activity was elevated upon the stimulation of T. gondii antigens, which was mitigated by co-transfection of mutant miR-7b promoter lacking peroxisome proliferator-activated receptor γ (PPARγ) target sites. Additionally, miR-7b mimics diminished Sp1 expression, while miR-7b inhibitors elevated its expression. miR-7b mimics deceased the fluorescence activity of Sp1 3' untranslated region (3' UTR), but it failed to impact the fluorescence activity upon the co-transfection of mutant Sp1 3' UTR lacking miR-7b target site. CONCLUSIONS: T. gondii infection and antigens promote miR-7b transcription but inhibit Foxp3 protein and gene levels. T. gondii antigens promote miR-7b promoter activity by a PPARγ-dependent mechanism. miR-7b directly binds to Sp1 3' UTR to repress Sp1 expression. Understanding the regulatory functions by which T. gondii-induced miR-7b suppresses Foxp3 expression can provide new perspectives for the possible therapeutic avenue of T. gondii-induced adverse pregnancy outcomes.

The application of extracorporeal membrane oxygenation in emergent airway management - a single-center retrospective study.

BACKGROUND: Emergent airway occurrences pose a significant threat to patient life. Extracorporeal membrane oxygenation (ECMO) has been proven to be an effective method for managing emergent airways. METHODS: A retrospective analysis was conducted on all patients receiving ECMO as an adjunct for emergent airway management from January 2018 to December 2022 at the People's Hospital of Zhongshan City. We collected the basic information of the patients, their blood gas data before and after ECMO, the related parameters of ECMO, and the outcome and then analyzed and summarized these data. RESULTS: Six patients, with an average age of 51.0(28-66) years, received veno-venous (VV)- ECMO as an adjunct due to emergent airway issues. The average ECMO support duration was 30.5(11-48) hours. All six patients were successfully weaned off ECMO support, with five (83.3%) being successfully discharged after a hospital stay of 15.5(7-55) days. All six patients underwent VV-ECMO through femoral-internal jugular vein cannulation. Among these, five patients, whose airway obstruction was due to hemorrhage, underwent a non-anticoagulant ECMO strategy with no recorded thrombotic events. CONCLUSIONS: The rapid establishment of ECMO support is aided by the establishment of a standardized ECMO initiation protocol and the formation of a multidisciplinary rapid-response ECMO team, which is particularly crucial for emergent airway management. When airway obstruction results from hemorrhagic factors, the early adoption of a non-anticoagulant ECMO strategy can be considered when implementing VV-ECMO.

Infiltrated 2D/3D Heterojunction with Tunable Electric Field Landscape for Robust Inverted Perovskite Solar Cells with over 24% Efficiency.

In inverted perovskite solar cells, conventional planar 2D/3D perovskite heterojunctions typically exhibit a type-II band alignment, where the electric field tends to drive the electron motion in the opposite direction to the direction of electron transfer. Here, a 2D/3D gradient heterojunction is developed by allowing the 2D perovskite to infiltrate the 3D perovskite surface along the grain boundaries using the interaction between the organic cation of the 2D perovskite and the pseudohalogen thiocyanate ion (SCN-), which has the ability to diffuse downward. The infiltrated 2D perovskite not only fills the gaps of grain boundaries with improved structural stability, but it also reconstructs the original landscape of the electric field toward the n-doped surface to enable more rapid electron transfer and weaken the adverse type-II band alignment effect. Since 2D perovskite seals the GBs, the nonvolatile SCN- can accumulate at the top and bottom dual interfaces, releasing residual stress and significantly inhibiting nonradiative recombination. The device exhibits an excellent efficiency of 24.76% (certified 24.29%) and long-term stability that is >90% of the original PCE value after 800 h of heating at 85 °C or in high humidity (≈65%).

Tunable Multivalent Aptamer-Based DNA Nanostructures To Regulate Multiheteroreceptor-Mediated Tumor Recognition.

Precise mapping and regulation of cell surface receptors hold immense significance in disease treatment, such as cancer, infection, and neurodisorders, but also face enormous challenges. In this study, we designed a series of adjustable multivalent aptamer-based DNA nanostructures to precisely control their interaction with receptors in tumor cells. By profiling surface receptors on 12 cell lines using 10 different aptamers, we generated a heatmap that accurately distinguished between various tumor types based on multiple markers. We then incorporated these aptamers onto DNA origami structures to regulate receptor recognition, with patch-like structures demonstrating a tendency to be trapped on the cell surface and with tube-like structures showing a preference for internalization. Through precise control of aptamer species, valence, and geometric patterns, we found that multiheteroreceptor-mediated recognition not only favored the specific binding of nanostructures to tumor cells but also greatly enhanced intracellular uptake by promoting clathrin-dependent endocytosis. Specifically, we achieved over 5-fold uptake in different tumor cells versus normal cells using tube-like structures modified with different diheteroaptamer pairs, facilitating targeted drug delivery. Moreover, patch-like structures with triheteroaptamers guided specific interactions between macrophages and tumor cells, leading to effective immune clearance. This programmable multivalent system allows for the precise regulation of cell recognition using multiple parameters, demonstrating great potential for personalized tumor treatment.

Simultaneous real-time detection of fractional exhaled nitric oxide and end-tidal carbon dioxide by quantum cascade laser absorption spectroscopy.

The simultaneous detection of fractional exhaled nitric oxide (FeNO) and end-tidal carbon dioxide (ETCO2) is of great importance for the distinguishing and diagnosis of asthma and chronic obstructive pulmonary disease (COPD), providing more comprehensive information on respiratory disorders. This work demonstrates a simultaneous ETCO2 and FeNO detection system based on quantum cascade laser absorption spectroscopy (QCLAS) technology was presented. The system employs wavelength modulation spectroscopy (WMS) technology and the Herriott multi-pass cell, achieving a detection limit of 2.82 ppb for nitric oxide (NO) and 0.05 % for carbon dioxide (CO2). Real-time exhalation measurements were performed on volunteers with varying ETCO2 and FeNO levels, and the results of the test can accurately distinguish whether the corresponding volunteer was healthy, had asthma or COPD. The effect of exhalation flow rate on the concentration of the two gases was explored. A range of expiratory flow rates were tested in the flow rate interval from 1 to 4 L/min, and there was always an inverse relationship between expiratory flow rate and FeNO concentration, but flow rate changes did not affect ETCO2 concentration. The results indicate that this detection system can simultaneously and effectively measure ETCO2 and FeNO concentrations in real-time.

Candidatus Accumulibacter use fermentation products for enhanced biological phosphorus removal.

Previous research suggested that two major groups of polyphosphate-accumulating organisms (PAOs), i.e., Ca. Accumulibacter and Tetrasphaera, play cooperative roles in enhanced biological phosphorus removal (EBPR). The fermentation of complex organic compounds by Tetrasphaera provides carbon sources for Ca. Accumulibacter. However, the viability of the fermentation products (e.g., lactate, succinate, alanine) as carbon sources for Ca. Accumulibacter and their potential effects on the metabolism of Ca. Accumulibacter were largely unknown. This work for the first time investigated the capability and metabolic details of Ca. Accumulibacter cognatus clade IIC strain SCUT-2 (enriched in a lab-scale reactor with a relative abundance of 42.8%) in using these fermentation products for EBPR. The enrichment culture was able to assimilate lactate and succinate with the anaerobic P release to carbon uptake ratios of 0.28 and 0.36 P mol/C mol, respectively. In the co-presence of acetate, the uptake of lactate was strongly inhibited, since two substrates shared the same transporter as suggested by the carbon uptake bioenergetic analysis. When acetate and succinate were fed at the same time, Ca. Accumulibacter assimilated two carbon sources simultaneously. Proton motive force (PMF) was the key driving force (up to 90%) for the uptake of lactate and succinate by Ca. Accumulibacter. Apart from the efflux of proton in symport with phosphate via the inorganic phosphate transport system, translocation of proton via the activity of fumarate reductase contributed to the generation of PMF, which agreed with the fact that PHV was a major component of PHA when lactate and succinate were used as carbon sources, involving the succinate-propionate pathway. Metabolic models for the usage of lactate and succinate by Ca. Accumulibacter for EBPR were built based on the combined physiological, biochemical, metagenomic, and metatranscriptomic analyses. Alanine was shown as an invalid carbon source for Ca. Accumulibacter. Instead, it significantly and adversely affected Ca. Accumulibacter-mediated EBPR. Phosphate release was observed without alanine uptake. Significant inhibitions on the aerobic phosphate uptake was also evident. Overall, this study suggested that there might not be a simply synergic relationship between Ca. Accumulibacter and Tetrasphaera. Their interactions would largely be determined by the kind of fermentation products released by the latter.

Ultrasound-assisted fermentation of ginkgo kernel juice by Lactiplantibacillus plantarum: Microbial response and juice composition development.

This study is aimed to explore the feasibility of ultrasound on enhancing the fermentation properties of ginkgo kernel juice by Lactiplantibacillus plantarum Y2. Specifically, ultrasound at 20 kHz and different intensities (mild ultrasound intensity-84.42 W/L, moderate ultrasound intensity-115.50 W/L, high ultrasound intensity-173.88 W/L) with a pulse mode were applied to facilitate the fermentation process. The number of viable cells of Lactiplantibacillus plantarum Y2 increased by 5.06, 5.05 and 2.19% in the sonicated groups at 173.88, 115.50 and 84.42 W/L, compared with the non-sonicated juice after 24-h fermentation. Furthermore, mild intensity ultrasonication improved the permeability of the cell membrane, which is beneficial for the metabolism of phenolics, amino acids and organic acids. Ultrasonication increased in-vitro antioxidant activity of fermented ginkgo kernel juice by promoting the metabolism of phenolic acids, such as ferulic acid, chlorogenic and caffeic acids. At the end of fermentation, the sonicated group at 84.42 W/L has the maximum consumptions of total sugars and proteins (increased by 12.52 and 18.73%). Moreover, the reduction rate of the poison material 4'-O-methylpyridoxine (MPN) in ginkgo kernel juice increased by more than 16.40% with ultrasound treatment at 173.88 W/L after the fermentation for 48 h. Overall, ultrasound can improve the metabolizations of Lactobacillus plantarum and reduce the toxic substances, which promoted the nutritional value and flavors of ginkgo kernel juice.

Low-intensity pulsed ultrasound of different intensities differently affects myocardial ischemia/reperfusion injury by modulating cardiac oxidative stress and inflammatory reaction.

Introduction: The prevalence of ischemic heart disease has reached pandemic levels worldwide. Early revascularization is currently the most effective therapy for ischemic heart diseases but paradoxically induces myocardial ischemia/reperfusion (MI/R) injury. Cardiac inflammatory reaction and oxidative stress are primarily involved in the pathology of MI/R injury. Low-intensity pulsed ultrasound (LIPUS) has been demonstrated to reduce cell injury by protecting against inflammatory reaction and oxidative stress in many diseases, including cardiovascular diseases, but rarely on MI/R injury. Methods: This study was designed to clarify whether LIPUS alleviates MI/R injury by alleviating inflammatory reaction and oxidative stress. Simultaneously, we have also tried to confirm which intensity of the LIPUS might be more suitable to ameliorate the MI/R injury, as well as to clarify the signaling mechanisms. MI/R and simulated ischemia/reperfusion (SI/R) were respectively induced in Sprague Dawley rats and human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). LIPUS treatment, biochemical measurements, cell death assay, estimation of cardiac oxidative stress and inflammatory reaction, and protein detections by western blotting were performed according to the protocol. Results: In our study, both in vivo and in vitro, LIPUS of 0.1 W/cm2 (LIPUS0.1) and 0.5 W/cm2 (LIPUS0.5) make no significant difference in the cardiomyocytes under normoxic condition. Under the hypoxic condition, MI/R injury, inflammatory reaction, and oxidative stress were partially ameliorated by LIPUS0.5 but were significantly aggravated by LIPUS of 2.5 W/cm2 (LIPUS2.5) both in vivo and in vitro. The activation of the apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK) pathway in cardiomyocytes with MI/R injury was partly rectified LIPUS0.5 both in vivo and in vitro. Conclusion: Our study firstly demonstrated that LIPUS of different intensities differently affects MI/R injury by regulating cardiac inflammatory reaction and oxidative stress. Modulations on the ASK1/JNK pathway are the signaling mechanism by which LIPUS0.5 exerts cardioprotective effects. LIPUS0.5 is promising for clinical translation in protecting against MI/R injury. This will be great welfare for patients suffering from MI/R injury.

TREM2 expression promotes liver and peritoneal M2 macrophage polarization in mice infected with Schistosoma japonicum.

Schistosomiasis is a tropical parasitic disease that damages the liver and poses a serious threat to human health. Macrophages play a key role in the development of liver granulomas and fibrosis by undergoing polarization from M1 to M2 type during schistosomiasis. Therefore, regulating macrophage polarization is important for controlling pathological changes that occur during this disease. Triggering receptor expressed on myeloid cells 2 (TREM2) expressed on the surface of macrophages, dendritic cells and other immune cells has been shown to play a role in inhibiting inflammatory responses and regulating M2 macrophage polarization, however its role in macrophage polarization in schistosomiasis has not been investigated. In this study, we confirmed that TREM2 expression was upregulated in the livers and peritoneal macrophages of mice infected with Schistosoma japonicum. Moreover, the TREM2 expression trend correlated with the expression of M2 macrophage polarization-related molecules in the liver tissues of S. japonicum-infected mice. Using Trem2-/- mice, we also showed that Trem2 deletion inhibited Arg1 and Ym1 expression in liver tissues. Trem2 deletion also increased the number of F4/80 + CD86+ cells in peritoneal macrophages of infected mice. In summary, our study suggests that TREM2 may be involved in M2 macrophage polarization during schistosomiasis.

Stimuli-Responsive PROTACs for Controlled Protein Degradation.

Proteolysis Targeting Chimeras (PROTACs) represent a promising therapeutic modality to address undruggable and resistant issues in drug discovery. However, potential on-target toxicity remains clinically challenging. We developed a generalized caging strategy to synthesize a series of stimuli-responsive PROTACs (sr-PROTACs) with diverse molecular blocks bearing robust and cleavable linkers, presenting "turn on" features in manipulating protein degradation. By leveraging pathological cues, such as elevated ROS, phosphatase, H2 S, or hypoxia, and external triggers, such as ultraviolet light, X-Ray, or bioorthogonal reagents, we achieved site-specific activation and traceless release of original PROTACs through de-caging and subsequent self-immolative cleavage, realizing selective uptake and controlled protein degradation in vitro. An in vivo study revealed that two sr-PROTACs with phosphate- and fluorine-containing cages exhibited high solubility and long plasma exposure, which were specifically activated by tumor overexpressing phosphatase or low dosage of X-Ray irradiation in situ, leading to efficient protein degradation and potent tumor remission. With more reactive biomarkers to be screened from clinical practice, our caging library could provide a general tool to design activatable PROTACs, prodrugs, antibody-drug conjugates, and smart biomaterials for personalized treatment, tissue engineering or regenerative medicine.