SENP3 mediates the deSUMOylation and degradation of YAP1 to regulate the progression of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a prevalent malignancy in women, casting a formidable shadow on their well-being. Positioned within the nucleolus, SUMO-specific protease 3 (SENP3) assumes a pivotal role in the realms of development and tumorigenesis. However, the participation of SENP3 in TNBC remains a mystery. Here, we elucidate that SENP3 exerts inhibitory effects on migration and invasion capacities, as well as on the stem cell-like phenotype, within TNBC cells. Further experiments showed that YAP1 is the downstream target of SENP3, and SENP3 regulates tumorigenesis in a YAP1-dependent manner. YAP1 is found to be SUMOylated and SENP3 deconjugates SUMOylated YAP1 and promotes degradation mediated by the ubiquitin-proteasome system. More importantly, YAP1 with a mutation at the SUMOylation site impedes the capacity of wild-type YAP1 in TNBC tumorigenesis. Taken together, our findings firmly establish the pivotal role of SENP3 in the modulation of YAP1 deSUMOylation, unveiling novel mechanistic insight into the important role of SENP3 in the regulation of TNBC tumorigenesis in a YAP1-dependent manner.

An integrated dual-gradient host facilitates oriented bottom-up lithium growth in lithium metal anodes.

Integrated gradient hosts, composed of poorly conductive frameworks on copper current collectors, have been extensively explored for the development of Li metal anodes (LMAs). Despite their potential, high Li nucleation overpotentials and slow interface kinetics often lead to inferior performance. Herein, we combine electrospinning and electrodeposition to create an integrated gradient host, namely OPAN/rGO-Cu2O/Cu. This involves electrodeposition of graphene oxide onto copper foil, reacting in situ to form a lithiophilic rGO-Cu2O layer, which is then covered with an oxidized polyacrylonitrile (OPAN) nanofiber layer, establishing conductivity and lithiophilicity dual gradients. The insulating OPAN top layer blocks electron transmission to the surface and prevents Li deposition, while the lithiophilic rGO-Cu2O layer facilitates Li ion transport to the bottom and reduces the nucleation barrier, both of which promote uniform Li deposition from bottom to top. As a result, the battery achieves an average coulombic efficiency of 98.4% over 500 cycles at 1 mA cm-2, and the symmetric cell sustains an ultra-long cycle life of 1600 h with a minimal polarization voltage of 12 mV. When paired with a LiFePO4 cathode, the full cell demonstrates a capacity retention of 92.6% after 300 cycles at 1 C, with an average capacity decay rate of just 0.025% per cycle. This innovative approach offers a promising pathway for developing high-performance LMAs.

Effectiveness of non-pharmaceutical interventions for COVID-19 in USA.

Worldwide, governments imposed non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic to contain the pandemic more effectively. We examined the effectiveness of individual NPIs in the United States during the first wave of the pandemic. Three types of analyses were performed. First, a prototypical Bayesian hierarchical model was employed to gauge the effectiveness of five NPIs and they are gathering restriction, restaurant capacity restriction, business closure, school closure, and stay-at-home order in the 42 states with over 100 deaths by the end of the wave. Second, we examined the effectiveness of the face mask mandate, the sixth and most controversial NPI by counterfactual modeling, which is a variant of the prototypical Bayesian hierarchical model allowing us to answer the question of what if the state had imposed the mandate or not. The third analysis used an advanced Bayesian hierarchical model to evaluate the effectiveness of all six NPIs in all 50 states and the District of Columbia, and thereby provide a full-scale estimation of the effectiveness of NPIs and the relative effectiveness of each NPI in the entire United States. Our results have enhanced the collective knowledge on the general effectiveness of NPIs in arresting the spread of COVID-19.

Realization of Joints of Aluminosilicate Glass and 6061 Aluminum Alloy via Picosecond Laser Welding without Optical Contact.

To achieve laser direct welding of glass and metal without optical contact is hard, owing to the large difference in thermal expansion and thermal conductivity between glass and metal and an insignificant melting area. In this study, the high-power picosecond pulsed laser was selected to successfully weld the aluminosilicate glass/6061 aluminum alloy with a gap of 35 ± 5 µm between glass and metal. The results show that the molten glass and metal diffuse and mix at the interface. No defects such as microcracks or holes are observed in the diffusion mixing zone. Due to the relatively large gap, the glass collapsed after melting and caulking, resulting in an approximately arc-shaped microcrack between modified glass and unmodified glass or weakly modified glass. The shape of the glass modification zone and thermal accumulation are influenced by the single-pulse energy and linear energy density of the picosecond laser during welding, resulting in variations in the number and size of defects and the shape of the glass modification zone. By reasonably tuning the two factors, the shear strength of the joint reaches 15.98 MPa. The diffusion and mixing at the interface and the mechanical interlocking effect of the glass modification zone are the main reasons for achieving a high shear strength of the joint. This study will provide reference and new ideas for the laser transmission welding of glass and metal in the non-optical contact conditions.

Effects of Inertial Flywheel Training vs. Accentuated Eccentric Loading Training on Strength, Power, and Speed in Well-Trained Male College Sprinters.

This study aimed to evaluate and compare the effects of inertial flywheel training and accentuated eccentric loading training on the neuromuscular performance of well-trained male college sprinters. Fourteen sprinters were recruited and randomly assigned to either the flywheel training (FWT, n = 7) group or the accentuated eccentric loading training (AELT, n = 7) group. The FWT group completed four sets of 2 + 7 repetitions of flywheel squats, whereas the AELT group performed four sets of seven repetitions of barbell squats (concentric/eccentric: 80%/120% 1RM). Both groups underwent an eight-week squat training program, with two sessions per week. A two-way repeated ANOVA analysis was used to find differences between the two groups and between the two testing times (pre-test vs. post-test). The results indicated significant improvements in all measured variables for the FWT group: 1RM (5.0%, ES = 1.28), CMJ (13.3%, ES = 5.42), SJ (6.0%, ES = 2.94), EUR (6.5%, ES = 4.42), SLJ (2.9%, ES = 1.77), and 30 m sprint (-3.4%, ES = -2.80); and for the AELT group: 1RM (6.3%, ES = 2.53), CMJ (7.4%, ES = 3.44), SJ (6.4%, ES = 2.21), SLJ (2.2%, ES = 1.20), and 30 m sprint (-3.0%, ES = -1.84), with the exception of EUR (0.9%, ES = 0.63, p = 0.134), showing no significant difference. In addition, no significant interaction effects between group and time were observed for 1RM back squat, SJ, SLJ, and 30 m sprint (p > 0.05). Conversely, a significant interaction effect between group and time was observed for both CMJ and EUR (p < 0.001); post hoc analysis revealed that the improvements in CMJ and EUR were significantly greater in the FWT group compared to the AELT group (p < 0.001). These findings indicate that both FWT and AELT are effective at enhancing lower-body strength, power, and speed in well-trained male college sprinters, with FWT being particularly more effective in promoting elastic energy storage and the full utilization of the stretch-shortening cycle.

Effects of undescribed iridoids in Patrinia punctiflora on insulin resistance in HepG2 cells.

Patrinia punctiflora is a medical and edible Chinese herb with high nutritional and medicinal value. The continuing study of its chemical constituents led to the isolation of six iridoids, which were previously unreported compounds, patriscabioins PU (1-6). Their structures were characterized and confirmed with NMR (1D & 2D), HRMS, IR and UV. Among them, compound 5 was screened to evaluate its insulin resistance activity on an IR-HepG-2 cell model. Compound 5 had no cytotoxicity compared with the control group and could promote glucose uptake in IR-HepG-2 cells. Through further mechanism studies, the undescribed compound 5 could increase the expression levels of PI-3 K, p-AKT, GLUT4 and p-GSK3ß proteins. Moreover, the expression of PEPCK and G6Pase proteins, which are key gluconeogenic enzymes, was also inhibited. Thus, compound 5 promotes the transfer of GLUT4 to the plasma membrane by activating the PI-3 K/AKT signaling pathway, at the same time, promotes glycogen synthesis and inhibits the onset of gluconeogenesis, which in turn ameliorates insulin resistance.

High throughput mRNA sequencing reveals potential therapeutic targets of Si-Ni-San in the pons for a stress-induced depression model.

Background: An accumulating body of research indicates that the pons is related to the occurrence of depression. Si-Ni-San (SNS) is a well-known Chinese herbal formula that is used to treat depression. Chinese herbal formulae have multiple therapeutic characteristics. Although it has been proven that SNS can exert antidepressant effects by improving changes in the limbic system, it is currently unclear whether SNS has therapeutic targets in the pons. This study aimed to explore the therapeutic targets of SNS in the pons for depression treatment. Materials and methods: Two experiments were conducted. In Experiment 1, 32 rats were divided into four groups: (1) a Control (C) group that received distilled water as a vehicle; (2) a Model (M) group that received the chronic unpredictable mild stress (CUMS) procedure and was administered distilled water; (3) a Stress + SNS (MS) group that received the CUMS procedure and was administered SNS dissolved in distilled water; and (4) a Stress + Fluoxetine (MF) group that received the CUMS procedure and was administered fluoxetine dissolved in distilled water. The open field test (OFT), the sucrose preference test (SPT), and the novel object recognition test (NOR) were performed to test the antidepressant effects of SNS. High-throughput mRNA sequencing (RNA-seq) was used to explore possible gene targets of SNS in the pons, and quantitative real-time PCR was performed to verify the results. High-performance liquid chromatography was used to detect neurotransmitters. Finally, correlation analyses were conducted between behaviors, genes expression, and neurotransmitters. In Experiment 2, 18 rats were divided into the same three groups as in Experiment 1: (1) C, (2) M, and (3) MS. fMRI was used to confirm whether SNS altered the pons in a rat model of depression. Results: SNS significantly improved sucrose preference in the SPT and TN-TO in the NOR compared to the M group (P < 0.05). RNA-seq filtered 49 differentially expressed genes(DEGs) that SNS could reverse in the pons of the CUMS depression model. Real-time PCR detected six genes, including Complexin2 (Cplx2), Serpinf1, Neuregulin1 (Nrg1), Annexin A1 (Anxa1), ß-arrestin 1 (Arrb1) and presenilin 1 (Psen1). SNS significantly reversed changes in the expression of Anxa1, Nrg1, and Psen1 caused by CUMS (P < 0.05), which is consistent with the DEGs results. Additionally, SNS significantly reversed norepinephrine (NE) changes in the pons. There were 18 noteworthy correlations between behavior, genes, and neurotransmitters (P < 0.05). fMRI showed that SNS can decrease the amplitude of low-frequency fluctuations (ALFF) in the pons of living depressed rats. Conclusion: The pons is an important target brain region for SNS to exert its antidepressant effects. SNS may improve pontine NE levels by regulating the Anxa1, Nrg1, and Psen1 genes, thereby exerting antidepressant effects and improving cognitive function.

Efficacy, safety, and tolerability of adjunctive Lacosamide therapy for focal seizures in young children aged ≥1 month to ≤4 years: A real-world study.

AIMS: To evaluate the efficacy, safety, and tolerability of adjunctive lacosamide therapy against focal seizures in young children (1 month - 4 years). METHODS: This non-randomized, open-label, and self-controlled real-world study included 105 children (1 month-4 years) with focal seizures treated with adjunctive lacosamide therapy at Children's Hospital of Chongqing Medical University. RESULTS: (1) The 50% response rates at 3, 6, 9, and 12 months of follow-up were 58.1%, 61.0%, 57.1%, and 56.2%, while the seizure-free rates were 27.6%, 34.3%, 32.4%, and 37.1%, respectively. The 50% response rate of the first addition of lacosamide for focal seizures was much higher than the second and later added treatment at 3 months (p = 0.038). After 1 year of follow-up, these children showed an improvement in neurodevelopmental levels (p < 0.05). (2) Lacosamide retention rate was 72.7% (64/88) after 1 year of follow-up. Lack of efficacy and serious adverse events were independent risk factors for the lacosamide retention rate. (3) During adjunctive lacosamide therapy, 13 (12.4%) patients reported adverse events and five (4.7%) patients withdrew due to adverse events, including vomiting drowsiness, ataxia (0.94%), neck itching with eczema (0.94%), irritability (1.88%), and gastrointestinal discomfort (0.94%). CONCLUSION: Adjunctive lacosamide therapy was effective, safe, and well-tolerated in young Chinese children with focal seizures in this study.

Digital anatomical features of morphological development in the atlantoaxial synchondroses in children aged 1 to 6 years old: a retrospective study of CT images.

OBJECTIVE: To investigate the anatomical indexes and anatomical positional indexes of the atlantoaxial synchondroses in normal Chinese Han children aged 1-6 years, and to analyze the changing law of the atlantoaxial cartilage union with the growth and development of age and its influence on the atlantoaxial ossification in children. METHODS: A retrospective collection of CT imaging of 160 cases of normal cervical spine in children aged 1 to 6 years old was conducted. The cases were divided into six age groups, with each group representing a one-year age range. Measure the morphological anatomical indicators and anatomical positional indicators of the atlantoaxial synchondroses. Record and statistically analyze the measurements of each indicator. RESULTS: Measurements were taken on various parameters of the atlantoaxial synchondroses. TD, SD, height, area, and perimeter all gradually decreased among the groups. Distance between bilateral atlantal anterolateral synchondroses increased gradually from Group A to Group F, while the angle formed along the long axis in the cross-section showed a decreasing trend. Distance between the axoid dentolateral synchondroses and between the neurocentral synchondroses increased gradually from Group A to Group F, with the angle value in the cross-section showing a gradual decrease, and distance from the odontoid apex increasing from Group A to Group F. CONCLUSIONS: The atlantoaxial synchondroses gradually decrease in size with age, and ossification levels increase with age, with faster ossification occurring during a 1-2 years-old period. The anterolateral synchondroses, dentolateral synchondroses, and neurocentral synchondroses all gradually ossify towards the lateral direction with increasing age.

Determination of the stability of sodium cyclamate during deep-frying using HPLC.

The oil used to fry food is often used multiple times to reduce costs. However, when foods containing sweeteners are processed in this way, the sweeteners may produce substances harmful to the body as a result of repeated frying at high temperatures. This article investigated the stability of sodium cyclamate during deep-frying by HPLC using a pre-column derivatization method. The results showed that cyclohexylamine was a decomposition product of a standard sample of sodium cyclamate when deep-fried at 200°C for 25 min. A pre-column derivatization/HPLC method was established to determine cyclohexylamine, a decomposition product of sodium cyclamate, under these conditions. Dansyl chloride was used as the derivatization reagent, the derivatization temperature was 60°C, the derivatization time was 20 min, the pH of sodium bicarbonate buffer solution was 11, and the concentration of dansyl chloride was 2.0 mg/mL. Detection was carried out by using an Agilent 1260 high-performance liquid chromatograph coupled with an ultraviolet detector. The ultraviolet detection wavelength was 254 nm, and the mobile phase was acetonitrile-1.0 g/L potassium dihydrogen phosphate solution at a flow rate of 1.0 mL/min. Gradient elution was adopted, the peak of the cyclohexylamine derivative appeared at a retention time of 17.75 min, and the peak area response value was the largest. The methodological validation analysis showed that the detection limit of cyclohexylamine was 0.5 mg/kg, the quantification limit was 2.0 mg/kg, and the spiked recoveries were in the range of 99.37-110.16%. The relative standard deviations (RSDs) were in the range of 0.17-1.26%. Four samples were tested and analyzed by the established method, and cyclohexylamine was not detected.

Hybrid metal halide family with color-time-dual-resolved phosphorescence for multiplexed information security applications.

Luminescent materials with engineered optical properties play an important role in anti-counterfeiting and information security technology. However, conventional luminescent coding is limited by fluorescence color or intensity, and high-level multi-dimensional luminescent encryption technology remains a critically challenging goal in different scenarios. To improve the encoding capacity, we present an optical multiplexing concept by synchronously manipulating the emission color and decay lifetimes of room-temperature phosphorescence materials at molecular level. Herein, we devise a family of zero-dimensional (0D) hybrid metal halides by combining organic phosphonium cations and metal halide tetrahedral anions as independent luminescent centers, which display blue phosphorescence and green persistent afterglow with the highest quantum yields of 39.9 % and 57.3 %, respectively. Significantly, the luminescence lifetime can be fine-tuned in the range of 0.0968-0.5046 µs and 33.46-125.61 ms as temporary time coding through precisely controlling the heavy atomic effect and inter-molecular interactions. As a consequence, synchronous blue phosphorescence and green afterglow are integrated into one 0D halide platform with adjustable emission lifetime acting as color- and time-resolved dual RTP materials, which realize the multiple applications in high-level anti-counterfeiting and information storage. The color-lifetime-dual-resolved encoding ability greatly broadens the scope of luminescent halide materials for optical multiplexing applications.

Highly Reversible "On-Off-On" Fluorescence Switch Governed by pH, Utilizing Bis(Benzimidazole) Derivatives with Varied Link Groups.

In this work, a series of dibenzimidazole derivatives 1-4, act as highly reversible colorimetric and fluorescent pH chemosensor, were designed and synthesized. Excellent reversible pH response of these sensors could be found by a specific pH change through obvious fluorescent color changes. The response is not affected by common cations (including Al3+, Cu2+, Ca2+, Cd2+, Co2+, Cr3+, Mg2+, Na+, K+, Ni2+, Pb2+ and Zn2+) and anions (including F-, Cl-, Br-, I-, ClO4-, H2PO4-, HSO4-, HCO3- and CH3COO-). Notably, these sensors can be reused more than 10 times without losing functionality. Unlike previous reports, the distinct properties of 1-4 are attributed to the varied link groups. Based on comprehensive experimental data and mechanistic analyses, it is concluded that sensors 1-4 are promising candidates for use as highly reversible "on-off-on" fluorescence switches under precise pH control.

Imaging Identifies Superior Inflammation Targeting of M1 Macrophages for Cryo-Shocked Cell Pulmonary Drug Delivery to Treat Acute Lung Injury.

In the realm of combating acute lung injury (ALI) induced by a myriad of triggers including sepsis, pneumonia, aspiration, trauma, and pancreatitis, macrophages emerge as crucial players. However, traditional treatments such as systemic administration of glucocorticoids come with the baggage of severe side effects, curtailing their utility. Enter an innovative solution: a biomimetic drug delivery system fashioned from cryo-shocked macrophages, tailored for pulmonary drug delivery. Positron emission tomography (PET) imaging has shed light on the remarkable targeting abilities of live M1 macrophages, showcasing their unparalleled efficacy in homing in on local inflammatory foci when contrasted with naive, M1, and M2 macrophages. Building upon this foundation, liquid nitrogen-treated (LNT) M1 macrophages are developed, engineered to preserve their inflammation-targeting prowess while sidestepping the release of pro-inflammatory cytokines. This breakthrough allows for the delivery of glucocorticoids directly to inflamed lung tissues, efficiently quelling inflammation and mitigating pulmonary edema while drastically reducing systemic drug exposure. Inspired by the effectiveness of live M1 macrophages, the potential of glucocorticoid-loaded LNT M1 macrophages are harnessed, utilizing them as a stealthy "Trojan horse" in the battle against pneumonia-induced ALI. This innovative approach holds promise as a safe and potent treatment avenue for acute lung injury.

The tissue virome of black-spotted frogs reveals a diversity of uncharacterized viruses.

Amphibians are an essential class in the maintenance of global ecosystem equilibrium, but they face serious extinction risks driven by climate change and infectious diseases. Unfortunately, the virus diversity harbored by these creatures has been rarely investigated. By profiling the virus flora residing in different tissues of 100 farmed black-spotted frogs (Rana nigromaculata) using a combination of DNA and RNA viromic methods, we captured 28 high-quality viral sequences covering at least 11 viral families. Most of these sequences were remarkably divergent, adding at least 10 new species and 4 new genera within the families Orthomyxoviridae, Adenoviridae, Nodaviridae, Phenuiviridae, and Picornaviridae. We recovered five orthomyxovirus segments, with three distantly neighboring two Chinese fish-related viruses. The recombination event of frog virus 3 occurred among the frog and turtle strains. The relative abundance and molecular detection revealed different tissue tropisms of these viruses, with the orthomyxovirus and adenoviruses being enteric and probably also neurotropic, but the new astrovirus and picornavirus being hepatophilic. These results expand the spectrum of viruses harbored by anurans, highlighting the necessity to continuously monitor these viruses and to investigate the virus diversity in a broader area with more diverse amphibian species.

Enhancing Interfacial Lithiophilicity and Stability with PVDF/In(NO3)3 Composite Separators for Durable Lithium Metal Anodes.

Separator modification is a promising method for advancing lithium metal anodes; however, achieving homogeneous lithium-ion flux and uniform plating/stripping processes remains challenging. In this work, we introduce a novel approach by developing a composite separator, termed PVDF-INO, which integrates In(NO3)3 (INO) into polyvinylidene fluoride (PVDF) to create a 12 µm thick layer. This addition significantly enhances the interaction between the separator and the electrolyte, creating a lithophilic matrix that ensures an even distribution of lithium ions. This uniform ion distribution promotes consistent lithium deposition and dissolution, resulting in a durable, dendrite-free lithium metal anode. Moreover, the PVDF-INO separator not only enhances the affinity with electrolytes but also maintains stable lithium-ion flux, which is essential for reliable and safe battery operation. Consequently, it sustains operation over 750 h in a Li||Li symmetric battery configuration, with a low overpotential of just 28 mV. Additionally, full cells equipped with LiFePO4 cathodes and the PVDF-INO separator exhibit superior cycling performance, maintaining a capacity retention of 92.9% after 800 cycles at 1 C. This work paves the way for significant advancements in the field of lithium metal batteries, offering a promising solution to longstanding energy storage challenges.

The Relationship between SNAP25 and Some Common Human Neurological Syndromes.

Over the years, research on the pathogenesis of neurological diseases has progressed slowly worldwide. However, as the incidence rate continues to increase and the disease gradually develops, early diagnosis and treatment have become a top priority. SANP25, a protein present on the presynaptic membrane and involved in neurotransmitter release, is closely related to the loss or abnormal expression of synapses and neurons. SNAP25 deficiency can lead to synaptic disorders and inhibit neurotransmitter release. Therefore, a large amount of literature believes that SNAP25 gene mutation is a risk factor for many neurological diseases. This review used advanced search on PubMed to conduct extensive article searches for relevant literature. The search keywords included SNAP25 and Alzheimer's disease, SNAP25 and Parkinson's disease, and so on. After reading and summarizing the previous papers, the corresponding conclusions were obtained to achieve the purpose of the review. The deficiency or variation of SNAP25 might be related to the onset of schizophrenia, epilepsy, attention deficit/hypoactivity disorder, bipolar disorder effective disorder, and autism. SNAP25 has been found to be used as a neuropathological marker for neurological diseases, which could be the target of diagnosis or treatment of Alzheimer's disease and Parkinson's disease. Cerebrospinal Fluid (CSF) or blood has been found to enable more effective drug development.

Continual medical image denoising based on triplet neural networks collaboration.

BACKGROUND: When multiple tasks are learned consecutively, the old model parameters may be overwritten by the new data, resulting in the phenomenon that the new task is learned and the old task is forgotten, which leads to catastrophic forgetting. Moreover, continual learning has no mature solution for image denoising tasks. METHODS: Therefore, in order to solve the problem of catastrophic forgetting caused by learning multiple denoising tasks, we propose a Triplet Neural-networks Collaboration-continuity DeNosing (TNCDN) model. Use triplet neural networks to update each other cooperatively. The knowledge from two denoising networks that maintain continual learning capability is transferred to the main-denoising network. The main-denoising network has new knowledge and can consolidate old knowledge. A co-training mechanism is designed. The main-denoising network updates the other two denoising networks with different thresholds to maintain memory reinforcement capability and knowledge extension capability. RESULTS: The experimental results show that our method effectively alleviates catastrophic forgetting. In GS, CT and ADNI datasets, compared with ANCL, the TNCDN(PromptIR) method reduced the average degree of forgetting on the evaluation index PSNR by 2.38 (39%) and RMSE by 1.63 (55%). CONCLUSION: This study aims to solve the problem of catastrophic forgetting caused by learning multiple denoising tasks. Although the experimental results are promising, extending the basic denoising model to more data sets and tasks will enhance its application. Nevertheless, this study is a starting point, which can provide reference and support for the further development of continuous learning image denoising task.

Mechanically Interlocked Polyrotaxane Networks with Collective Motions of Multiple Main-Chain Mechanical Bonds.

Type I main-chain polyrotaxanes (PRs) with multiple wheels threaded onto the axle are widely employed to design slide-ring materials. However, Type II main-chain PRs with axles threading into the macrocycles on the polymer backbones have rarely been studied, although they feature special topological structures and dynamic characteristics. Herein, we report the design and preparation of Type II main-chain PR-based mechanically interlocked networks (PRMINs), based on which the relationship between microscopic motion of mechanical bonds on the PRs and macroscopic mechanical performance of materials has been revealed. The representative PRMIN-2 exhibits a robust feature in tensile tests with high stretchability (1680 %) and toughness (47.5 MJ/m3). Moreover, it also has good puncture performance with puncture energy of 22.0 mJ. Detailed rheological measurements and coarse-grained molecular dynamics (CGMD) simulation reveal that the embedded multiple [2]rotaxane mechanical bonds on the PR backbones of PRMINs could undergo a synergistic long-range sliding motion under external force, with the introduction of collective dangling chains into the network. As a result, the synchronized motions of coherent PR chains can be readily activated to accommodate network deformation and efficiently dissipate energy, thereby leading to enhanced mechanical performances of PRMINs.

Sustainable succinic acid production from lignocellulosic hydrolysates by engineered strains of Yarrowia lipolytica at low pH.

Succinic acid (SA) is a valuable C4 platform chemical with diverse applications. Lignocellulosic biomass represents an abundant and renewable carbon resource for microbial production of SA. However, the presence of toxic compounds in pretreated lignocellulosic hydrolysates poses challenges to cell metabolism, leading to inefficient SA production. Here, engineered Yarrowia lipolytica Hi-SA2 was shown to utilize glucose and xylose from corncob hydrolysate to produce 32.6 g/L SA in shaking flasks. The high concentration of undetoxified hydrolysates significantly inhibited yeast growth and SA biosynthesis, with furfural identified as the key inhibitor. Through overexpressing glutathione synthetase encoding gene YlGsh2, the tolerance of engineered strain to furfural and toxic hydrolysate was significantly improved. In a 5-L bioreactor, Hi-SA2-YlGsh2 strain produced 45.34 g/L SA within 32 h, with a final pH of 3.28. This study provides a sustainable process for bio-based SA production, highlighting the efficient SA synthesis from lignocellulosic biomass through low pH fermentation.