Passive activity enhances residual control ability in patients with complete spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202508000-00024/figure1/v/2024-09-30T120553Z/r/image-tiff Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level. However, because of prolonged inactivity, initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway. A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation, as measured by surface electromyography. In this study, we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury. Eleven patients with chronic complete thoracic spinal cord injury were recruited. Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol. The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation. Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity, the difference was not statistically significant. These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.

Mass Spectrometry Probe Combined with Machine Learning to Capture the Relationship between Metabolites and Mitochondrial Complex Activity at the Whole-Cell Level.

Mitochondrial complex activity controls a multitude of physiological processes by regulating the cellular metabolism. Current methods for evaluating mitochondrial complex activity mainly focus on single metabolic reactions within mitochondria. These methods often require fresh samples in large quantities for mitochondria purification or intact mitochondrial membranes for real-time monitoring. Confronting these limitations, we shifted the analytical perspective toward interactive metabolic networks at the whole-cell level to reflect mitochondrial complex activity. To this end, we compiled a panel of mitochondrial respiratory chain-mapped metabolites (MRCMs), whose perturbations theoretically provide an overall reflection on mitochondrial complex activity. By introducing N-dimethyl-p-phenylenediamine and N-methyl-p-phenylenediamine as a pair of mass spectrometry probes, an ultraperformance liquid chromatography-tandem mass spectrometry method with high sensitivity (LLOQ as low as 0.2 fmol) was developed to obtain accurate quantitative data of MRCMs. Machine learning was then combined to capture the relationship between MRCMs and mitochondrial complex activity. Using Complex I as a proof-of-concept, we identified NADH, alanine, and phosphoenolpyruvate as metabolites associated with Complex I activity based on the whole-cell level. The effectiveness of using their concentrations to reflect Complex I activity was further validated in external data sets. Hence, by capturing the relationship between metabolites and mitochondrial complex activity at the whole-cell level, this study explores a novel analytical paradigm for the interrogation of mitochondrial complex activity, offering a favorable complement to existing methods particularly when sample quantities, type, and treatment timeliness pose challenges. More importantly, it shifts the focus from individual metabolic reactions within mitochondria to a more comprehensive view of an interactive metabolic network, which should serve as a promising direction for future research into the functional architecture between mitochondrial complexes and metabolites.

Thinking Induced by Acute Kidney Injury of Diquat Poisoning: Cases Report.

Diquat poisoning is a fatal condition that is becoming increasingly common. The mortality risk of patients taking lethal doses of diquat is extremely high. It typically leads to rapid dysfunction of multiple organs, including the kidneys, heart, lungs, and brain. Acute kidney injury is usually the first manifestation of this poisoning. However, the optimal treatment strategy for diquat poisoning remains uncertain. Additionally, the mechanism of multiple organ dysfunction syndrome caused by diquat poisoning may resemble the progression of sepsis. In this report, we present 3 cases of diquat poisoning, all of which resulted in death. We emphasize that acute kidney injury is the primary cause of death, and suggest that some strategies used in the treatment of sepsis could be beneficial in managing diquat poisoning-induced acute kidney injury.

Pterosin B improves cognitive dysfunction by promoting microglia M1/M2 polarization through inhibiting Klf5/Parp14 pathway.

BACKGROUND: Pterosin B (PB) exhibits strong neuroprotective effects in vitro, but its therapeutic effect and underlying mechanism on Alzheimer's disease (AD) remain elusive. PURPOSE: This study aimed to investigate the anti-AD effect and mechanism of PB. STUDY DESIGN: The therapeutic effect and mechanism of PB were investigated in APP/PS1 mice and lipopolysaccharide (LPS)-induced BV-2 cells. METHODS: After 8 weeks of oral administration of PB or donepezil, the cognitive function was assessed using behavioral tests. Pathological damage was evaluated using histological analysis and immunohistochemical staining. Flow cytometry was applied to detect M1/M2 polarization. The expression levels of glycolysis- and oxidative phosphorylation-related proteins as well as enzyme activities were determined using Western blot and biochemical kits, respectively. The levels of inflammatory cytokines and Kruppel-like factor 5 (Klf5) were measured using enzyme-linked immunosorbent assay. AD biomarkers in serum were analyzed using single-molecular array. RNA sequencing identified the downstream molecules of Klf5, and interaction was evaluated using dual-luciferase reporter assay. RESULTS: Our findings demonstrated that PB effectively ameliorated cognitive impairment and reduced pathological damage in APP/PS1 mice. Furthermore, PB facilitated the transition of the phenotype of LPS-induced BV-2 cells from M1 to M2 by modulating metabolic reprogramming. Additionally, Klf5 had high expression levels in the serum of patients with AD, which strongly correlated with cognitive performance and AD biomarkers. PB downregulated Klf5 expression both in vitro and in vivo. Subsequently, poly-ADP ribosyl polymerase 14 (Parp14) was identified as a downstream molecule of Klf5 involved in regulating metabolic reprogramming, and PB regulated microglia M1/M2 polarization by inhibiting the Klf5/Parp14 pathway. CONCLUSION: The findings suggested that PB ameliorated cognitive dysfunction in AD by modulating microglia M1/M2 polarization via inhibiting Klf5/Parp14 pathway.

Interaction and dynamic changes of microbial communities and volatile flavor compounds during the fermentation process of coffee flower rice wine.

To develop a unique flavor of rice wine, coffee flowers (by-products of the coffee industry) were added because of their biologically active compounds that are conducive to health, and the fermentation parameters were optimized. In addition, the dynamic changes of microbial communities and volatile flavor compounds (VFCs) during the different fermentation stages were investigated. After the optimization of the fermentation parameters, a novel product, i.e., the coffee flower rice wine (CFRW), was obtained with a bright yellow transparent, fragrant, and harmonious aroma and mellow and refreshing taste by sensory evaluation, when 4.62% of the coffee flowers and 1.93% koji were added and fermented at 24.10°C for 3.88 days. The results showed that Lactococcus was the dominant bacteria, accounting for 87.0-95.7%, while Rhizopus and Cladosporium were the main fungi, accounting for 68.2% and 11.3% on average, respectively, in the fermentation process of the CFRW. Meanwhile, twenty-three VFCs were detected in the CFRW, which included three alcohols, six terpenes, ten esters, three aromatics, and one furan. The correlation analysis revealed that there were 16 significant positive correlations and 23 significant negative correlations between the bacterium and VFCs (|ρ| > 0.6, p < 0.05), while there were 12 significant positive correlations and one significant negative correlation between the fungi and VFCs (|ρ| > 0.6, p < 0.05). Furthermore, five VFCs, including linalool, geraniol, ethyl acetate, 1-hexanol, and 3-methyl-1-butanol, contributed vital flavors to the CFRW, and they were all significantly negatively correlated with the changes of Massilia and Acinetobacter (|ρ| > 0.6, p < 0.05). Moreover a significant positive correlation was found between the relative abundance of Lactococcus and the contents of 3-methyl-1-butanol and ethyl acetate (|ρ| > 0.6, p < 0.05). Therefore, this study provides a valuable theoretical basis for further improving the quality and production technology of CFRW.

Characterization of anti-EBNA-1 antibodies and exploration of their molecular mimicry potential in an EBV-infected Sjögren's syndrome patient.

There is a potential link between autoimmune diseases and Epstein-Barr virus (EBV) infections, with EBV playing a substantial role in the onset of Sjögren's syndrome (SjS). Some EBV proteins could mimic host self-antigens post-infection, leading to molecular mimicry. This similarity may cause the immune system to attack its tissues mistakenly. Among the various proteins associated with EBV, nuclear antigen 1 (EBNA-1) is essential for the latent replication of infected cells and is prevalent in all EBV-related diseases. In the study, single-chain variable fragment (scFv) antibodies targeting EBNA-1 were isolated using phage display technology from a primary SjS patient who also had a chronic active EBV infection. The specific clones were enriched after panning, and the binding activity of selected scFvs targeting EBNA-1 was confirmed. Sequence analysis indicated that the scFvs exhibiting positive signals could be grouped into five clones, all of which used homologous heavy chain V regions derived from germline Vh4-39, and two types of light chain V regions stemming from germline Vλ1-44 and Vλ3-15. These scFvs were found to exhibit a high degree of somatic mutations, likely indicative of antigen selection. Of the scFvs, P1-3 demonstrated the strongest binding affinity to EBNA-1, exhibiting a determined value of 7.3 x 10-8 M, and showed cross-reactivity to the SjS associated La/SSB self-antigen. The experimental results combined with AlphaFold 3 predictions revealed a potential epitope for scFv P1-3 binding to EBNA-1. Additionally, scFv P1-3 could also cross-bind to the modeled structure of La/SSB. We inferred a possible structural correlation between EBNA-1 and La/SSB involving an X2AX6PG epitope motif. This research contributes to our understanding of the structural basis of the interactions between antibodies and EBNA-1, shedding light on the VH and VL gene usage of anti-EBNA-1 antibodies in EBV-infected SjS patients and the potential origins of autoantibodies.

Huang Lian Jie Du decoction attenuated colitis via suppressing the macrophage Csf1r/Src pathway and modulating gut microbiota.

Introduction: Ulcerative colitis, a subtype of chronic inflammatory bowel disease (IBD), is characterized by relapsing colonic inflammation and ulcers. The traditional Chinese herbal formulation Huang Lian Jie Du (HLJD) decoction is used clinically to treat diarrhea and colitis. However, the mechanisms associated with the effects of treatment remain unclear. This study aims to elucidate the molecular mechanistic effects of HLJD formulation on colitis. Methods: Chronic colitis in mice was induced by adding 1% dextran sulfate sodium (DSS) to their drinking water continuously for 8 weeks, and HLJD decoction at the doses of 2 and 4 g/kg was administered orally to mice daily from the second week until experimental endpoint. Stool consistency scores, blood stool scores, and body weights were recorded weekly. Disease activity index (DAI) was determined before necropsy, where colon tissues were collected for biochemical analyses. In addition, the fecal microbiome of treated mice was characterized using 16S rRNA amplicon sequencing. Results: HLJD decoction at doses of 2 and 4 g/kg relieved DSS-induced chronic colitis in mice by suppressing inflammation through compromised macrophage activity in colonic tissues associated with the colony-stimulating factor 1 receptor (Csf1r)/Src pathway. Furthermore, the HLJD formula could modify the gut microbiota profile by decreasing the abundance of Bacteroides, Odoribacter, Clostridium_sensu_stricto_1, and Parasutterella. In addition, close correlations between DAI, colon length, spleen weight, and gut microbiota were identified. Discussion: Our findings revealed that the HLJD formula attenuated DSS-induced chronic colitis by reducing inflammation via Csf1r/Src-mediated macrophage infiltration, as well as modulating the gut microbiota profile.

Fast and Selective Cysteine Conjugation Using para-Quinone Methides.

An efficient and selective method for cysteine conjugation utilizing para-quinone methides (p-QMs) was developed. p-QM labeling exhibits high specificity toward the cysteine residue, as evidenced by its reactivity with various amino acid derivatives, peptides, and proteins. Notably, the p-QM-cysteine reactions display robust kinetics with rate constants up to 1.67 × 104 M-1·s-1. Furthermore, p-QM conjugation enables us to attach a fluorescent probe to a HER2 nanobody, resulting in selective labeling of HER2-positive SK-BR-3 cells.

A novel colorimetric and fluorometric dual-signal identification of crude baijiu based on La-CDs.

The correct classification of strong-flavored crude baijiu affects its quality and overall standard and is crucial for the intelligent development of the baijiu industry. In this work, we developed a novel optical sensing array using lanthanum-doped carbon dots (La-CDs). Using La-CDs with three metal complex dyes-chromium black T, alizarin red, and dimethylphenol orange-we were able to detect organic acids and tannic acid (TA) in crude baijiu in a way that was both colorimetric and fluorescent for the first time. Based on the indicator displacement (IDA) principle, organic acids competitively replace the dyes' binding sites on La3+, causing the dye colors to change to varying degrees. TA quenches the fluorescence of quantum dots through an internal filtering effect. We analyzed the data using pattern recognition algorithms such as HCA, PCA, and LDA, successfully classifying and identifying 16 types of strong-flavored crude baijiu, which included 10 types of carboxylic acids and various grades. In blind tests of 32 crude baijiu samples, the colorimetric method achieved a 94 % accuracy rate, while the fluorescence method achieved 100 %. The sensor demonstrates significant advantages in response speed.

Controlling Guest Diffusion by Local Dynamic Motion in Soft Porous Crystals to Separate Water Isotopologues and Similar Gases.

ConspectusThe precise and effective separation of similar mixtures is one of the fundamental issues and essential tasks in chemical research. In the field of gas/vapor separation, the size difference among the molecular pairs/isomers of light hydrocarbons and aromatic compounds is generally 0.3-0.5 Å, and the boiling-point difference is generally 6-15 K. These are necessary industrial raw materials and have great separation demands. Still, their separation mainly relies on energy-intensive distillation technology. On the other hand, remarkably similar substances such as oxygen/argon and isotopologues usually exhibit size differences of only 0-0.07 Å and boiling-point differences of only 1-3 K. Although their industrial separation can be realized, their efficiency is considerably low. Therefore, effectively separating remarkably similar mixtures is crucial in fundamental chemistry and industry, but it remains a significant challenge. Porous coordination polymers (PCPs) or metal-organic frameworks (MOFs) are emerging materials platforms for designing adsorbents for separating similar mixtures. However, the reported PCPs did not work well for separating remarkably similar substances. The framework structures of the mainstream PCPs remain unchanged (rigid) or significantly change (globally flexible) upon adsorption. However, rigid and globally flexible PCPs find controlling the pore aperture in subangstrom precision challenging, a prerequisite for distinguishing remarkably similar substances. Thus, novel mechanisms and materials design principles are urgently needed to realize PCPs-based adsorptive separation of remarkably similar mixtures.To confront the obstacles in separating remarkably similar mixtures, our group started contributing to this field in 2017. We employed locally flexible PCPs as the materials designing platform, whose local motions of the side substituent groups potentially regulate the pore apertures to design and control the gas/vapor diffusion in PCPs. Specifically, we encoded dynamic flipping molecular motions into the diffusion-regulatory gate functionality. The ligands were designed by integrating carboxylic coordination groups with nonplanar fused-ring moieties, with the latter moieties exhibiting flipping motion around their equilibrium positions with small energy increases. Such local motions of ligands lead to the dynamic opening and blocking of PCP channels, thus termed flipping dynamic crystals (FDCs). FDCs feature distinctive temperature-responsive adsorption behaviors due to the competition of thermodynamics and kinetics under diffusion regulation, enabling differentiation of remarkably similar mixtures by each gate-admission temperature much higher than the boiling-point temperature of each component. Even when the molecular sizes are the same in the water isotopologue mixtures, FDCs can separate each isotopologue by amplifying their diffusion-rate differences. Finally, by combining the thermodynamic and kinetic factors, FDCs achieve temperature-switched recognition of CO2/C2H2 and diffusion-rate sieving of C3H6/C3H8. Therefore, our work provides a platform for designing locally flexible PCPs by introducing subangstrom precision in flexibility. This opens up the feasibility of separating remarkably similar mixtures on scientific principles. In this Account, we summarize our above ongoing research contributions, including (i) the design of flipping ligands and FDCs, (ii) the characterization of flipping motions, (iii) the gas/isotopologue sorption behaviors, and (iv) the separation of gases and isotopologues. Overall, our studies offer a new aspect of soft porous crystals and provide future opportunities for relevant researchers in this field.

Thermal and Sono-Aqueous Reforming of Alcohols for Sustainable Hydrogen Production.

Hydrogen is a clean-burning fuel with water as its only by-product, yet its widespread adoption is hampered by logistical challenges. Liquid organic hydrogen carriers, such as alcohols from sustainable sources, can be converted to hydrogen through aqueous-phase reforming (APR), a promising technology that bypasses the energy-intensive vaporization of feedstocks. However, the hydrothermal conditions of APR pose significant challenges to catalyst stability, which is crucial for its industrial deployment. This review focuses on the stability of catalysts in APR, particularly in sustaining hydrogen production over extended durations or multiple reaction cycles. Additionally, we explore the potential of ultrasound-assisted APR, where sonolysis enables hydrogen production without external heating. Although the technological readiness of ultrasound-assisted or -induced APR currently trails behind thermal APR, the development of catalysts optimized for ultrasound use may unlock new possibilities in the efficient hydrogen production from alcohols.

Prevalence and genetic diversity of Parechovirus.

Human parechovirus (HPeV) is a common virus that can cause severe infections in newborns. Due to the limited knowledge of the prevalence of HPeV in different cities in China and the unknown association between HPeV infection and clinical characteristics of newborns, this research investigated the epidemiological and clinical characteristics of HPeV infection in hospitalized neonates in Changsha. From August to October 2023, 145 anal swab samples from 96 newborns and 38 pharyngeal swab samples from 33 newborns in the neonatal intensive care unit (NICU) were collected. The prevalence of HPeV was detected by reverse transcription-polymerase chain reaction (RT-PCR). The genomes of HPeV were sequenced and the viral protein 1 (VP1) region was used for genotyping. Phylogenetic analysis and recombination analysis of HPeV genome were performed. Finally, HPeV was detected in 10 out of 44 patients in October, all of them were HPeV-1. The sequenced 4 genomes of HPeV showed high genetic diversity with known strains. Additionally, a HPeV-1 recombinant strain was detected. Compared with HPeV negative patients, HPeV patients had higher prevalence of abdominal pain and diarrhea, intracranial hemorrhage, and purulent meningitis. Compared with HPeV negative patients, HPeV patients had higher peripheral blood lymphocytes, albumin, globulin, pH and lower peripheral blood neutrophils and hemoglobin. HPeV is an important viral cause of newborn infections and appears to be increasing in prevalence in recent years. Characteristic clinical pictures exist in HPeV infections, and further research is needed to accumulate more cases to obtain a comprehensive understanding of HPeV infections.

Stereocontrolled Hydrogenation of Conjugated Enones to Alcohols via Dual Iridium-Catalysis.

The concept of dual catalysis is an emerging area holding high potential in terms of preparative efficiency, yet faces severe challenges in compatibility of reaction conditions and interference of catalysts. The transition-metal catalyzed stereoselective hydrogenation of olefins and ketones typically proceeds under different reaction conditions and/or uses a different reductant. As a result, these two types of hydrogenations can normally not be performed in the same pot. Herein, the stereocontrolled hydrogenation of enones to saturated alcohols is described, enabled by orthogonal dual iridium catalysis, using molecular hydrogen for both reductions. In this one-pot procedure, N,P-iridium catalysts (hydrogenation active towards olefins) and NHC,P-iridium catalysts (hydrogenation active towards ketones) operated independently of one another allowing the construction of two contiguous stereogenic centers up to 99% ee, 99/1 d.r. Ultimately, by simple selection of the chirality of either ligands, the enone could be efficiently reduced to all four stereoisomers of the saturated alcohol in equally high stereopurity. This degree of stereocontrol for the synthesis of different stereoisomers by dual transition-metal catalyzed hydrogenation was previously not attained. The generality in substituted enones (alkyl, aryl, heteroaryl) demonstrate the wide applicability of this concept.

A machine-learning model of academic resilience in the times of the COVID-19 pandemic: Evidence drawn from 79 countries/economies in the PISA 2022 mathematics study.

BACKGROUND: Given that students from socio-economically disadvantaged family backgrounds are more likely to suffer from low academic performance, there is an interest in identifying features of academic resilience, which may mitigate the relationship between disadvantaged socio-economic status and academic performance. AIMS: This study sought to combine machine learning and explainable artificial intelligence (XAI) technique to identify key features of academic resilience in mathematics learning during COVID-19. MATERIALS AND METHODS: Based on PISA 2022 data in 79 countries/economies, the random forest model coupled with Shapley additive explanations (SHAP) value technique not only uncovered the key features of academic resilience but also examined the contributions of each key feature. RESULTS: Findings indicated that 35 features were identified in the classification of academically resilient and non-academically resilient students, which largely validated the previous academic resilient framework. Notably, gender differences were shown in the distribution of some key features. Research findings also indicated that resilient students tended to have a stable emotional state, high levels of self-efficacy, low levels of truancy and positive future aspirations. DISCUSSION: This study has established a research paradigm essentially methodological in nature to bridge the gap between psychological theories and big data in the field of educational psychology. CONCLUSION: To sum up, our study shed light on the issues of education equity and quality from a global perspective in the times of the COVID-19 pandemic.

The biphasic role of the infrapatellar fat pad in osteoarthritis.

Osteoarthritis (OA) is a progressive degenerative disease resulting in joint deterioration. It is a whole organ disease characterized by cartilage degeneration and varying degrees of synovitis, involving pathological changes in all joint tissues, such as cartilage, subchondral bone, ligaments, meniscus, synovium, and infrapatellar fat pad (IPFP). IPFP is the largest adipose tissue structure in the knee joint and is composed of fat cells, immune cells and blood vessels. Moreover, IPFP is located close to the cartilage and bone surface so that it may reduce the impact of loading and absorb forces generated through the knee joint, and may have a protective role in joint health. IPFP has been shown to release various cytokines and adipokines that play pro-inflammatory and pro-catabolic roles in cartilage, promoting OA progression. Intra-articular injections of IPFP-derived mesenchymal stem cells and exosomes have been shown to reduce pain and prevent OA progression in patients with knee OA. Previous studies have shown that IPFP has a biphasic effect on OA progression. This article reviews the latest research progress of IPFP, discusses the role and mechanism of IPFP in OA, provide new intervention strategies for the treatment of OA. This article will also discuss the handling of IPFP during the procedure of total knee arthroplasty.

GmBSK1-GmGSK1-GmBES1.5 regulatory module controls heat tolerance in soybean.

INTRODUCTION: Heat stress poses a severe threat to the growth and production of soybean (Glycine max). Brassinosteroids (BRs) actively participate in plant responses to abiotic stresses, however, the role of BR signaling pathway genes in response to heat stress in soybean remains poorly understood. OBJECTIVES: In this study, we investigate the regulatory mechanisms of GmBSK1 and GmBES1.5 in response to heat stress and the physiological characteristics and yield performance under heat stress conditions. METHODS: Transgenic technology and CRISPR/Cas9 technology were used to generated GmBSK1-OE, GmBES1.5-OE and gmbsk1 transgenic soybean plants, and transcriptome analysis, LUC activity assay and EMSA assay were carried out to elucidate the potential molecular mechanism underlying GmBSK1-GmBES1.5-mediated heat stress tolerance in soybean. RESULTS: CRISPR/Cas9-generated gmbsk1 knockout mutants exhibited increased sensitivity to heat stress due to a reduction in their ability to scavenge reactive oxygen species (ROS). The expression of GmBES1.5 was up-regulated in GmBSK1-OE plants under heat stress conditions, and it directly binds to the E-box motif present in the promoters of abiotic stress-related genes, thereby enhancing heat stress tolerance in soybean plants. Furthermore, we identified an interaction between GmGSK1 and GmBES1.5, while GmGSK1 inhibits the transcriptional activity of GmBES1.5. Interestingly, the interaction between GmBSK1 and GmGSK1 promotes the localization of GmGSK1 to the plasma membrane and releases the transcriptional activity of GmBES1.5. CONCLUSION: Our findings suggest that both GmBSK1 and GmBES1.5 play crucial roles in conferring heat stress tolerance, highlighting a potential strategy for breeding heat-tolerant soybean crops involving the regulatory module consisting of GmBSK1-GmGSK1-GmBES1.5.

Zinc Enhances Cadmium Accumulation in Shoots of Hyperaccumulator Solanum nigrum by Improving ATP-Dependent Transport and Alleviating Toxicity.

Solanum nigrum is a cadmium (Cd) and zinc (Zn) accumulator with potential for phytoextraction of soil contaminated with heavy metals. However, how Zn affects Cd accumulation in S. nigrum remains unclear. In this study, S. nigrum seedlings were treated with 100 µmol·L-1 Zn (Zn100), 100 µmol·L-1 Cd (Cd100), and the Zn and Cd combination (Zn100+Cd100) for 10 days under hydroponic culture. Compared with Cd100, the Cd content in stems, leaves, and xylem saps was 1.8, 1.6, and 1.3 times more than that in Zn100+Cd100, respectively. In addition, the production of reactive oxygen species in leaves was significantly upregulated in Cd100 compared with the control, and it was downregulated in Zn100. Comparative analyses of transcriptomes and proteomes were conducted with S. nigrum leaves. Differentially expressed genes (DEGs) were involved in Cd uptake, transport, and sequestration, and the upregulation of some transporter genes of Zn transporters (ZIPs), a natural resistance associated macrophage protein (Nramp1), a metal-nicotianamine transporter (YSL2), ATP-binding cassette transporters (ABCs), oligopeptide transporters (OPTs), and metallothionein (MTs) and glutathione S-transferase (GSTs) genes was higher in Zn100+Cd100 than in Cd100. In addition, differentially expressed proteins (DEPs) involved in electron transport chain, ATP, and chlorophyll biosynthesis, such as malate dehydrogenases (MDHs), ATPases, and chlorophyll a/b binding proteins, were mostly upregulated in Zn100. The results indicate that Zn supplement increases Cd accumulation and tolerance in S. nigrum by upregulating ATP-dependent Cd transport and sequestration pathways.

Ultra-smooth processing of lithium niobate for outstanding mid-infrared transmittance.

The fabrication of anti-reflection (AR) subwavelength structures (SWSs) of lithium niobate (LN) is a challenging but rewarding task in mid-infrared LN laser systems. However, there are still some issues with the high-quality processing and fabrication of bifacial AR SWSs. Herein, a novel, to the best of our knowledge, approach to the fabrication of SWSs was proposed, which includes femtosecond laser ablation followed by wet etching and thermal annealing. The fabricated structures exhibit high surface quality (Ra = 0.08 nm) and uniformity. According to the experimental and simulated results, the transmittance of the mid-infrared AR SWSs with a period of 1.8 µm could be improved from 78% to 87% in the 3.6-5 µm band. Furthermore, the double-sided construction enabled a transmittance of up to 90%. The results have great potential in the promotion of the development of mid-infrared laser systems and LN-based photonics.

Lactate-upregulated ARG2 expression induces cellular senescence in fibroblast-like synoviocytes of osteoarthritis via activating the mTOR/S6K1 signaling pathway.

Cellular senescence was implicated in the pathogenesis of age-related diseases such as osteoarthritis (OA). Increasing evidence suggests that alterations in the OA joint microenvironment play a crucial role in the pathogenesis of OA. This study aims to establish a clear link between the impact of accumulated lactate on the senescence of fibroblast-like synoviocytes (FLS) within the OA microenvironment. OA models and models with intra-articular injection of lactate were established in rat models, histological analyses were performed. Human OA-FLS treated with lactate was analyzed by mRNA sequencing, senescence related experiments and underlying signaling pathway activation were comprehensively evaluated. This study confirmed that OA models and lactate-injection models exhibited higher synovitis scores. Enrichment analyses indicated dysregulated cell cycle and cellular senescence pathways in OA-FLS treated with lactate. Lactate significantly up-regulated arginase 2 (ARG2) expression and promoted OA-FLS senescence, including G1/S arrest, increased reactive oxygen species and ß-galactosidase production, high expression of senescence-associated secretory phenotype factors, which could be attenuated by siRNA-Arg2. The ARG2-mTOR/S6K1 axis was identified as a potential signaling for lactate-induced OA-FLS senescence, and activated mTOR/S6K1 signaling could be reduced by siRNA-Arg2, rapamycin (mTOR inhibitor), and LY294002 (PI3K inhibitor). Our study provides novel targets and insights for OA therapies.