Overexpression of the WRKY transcription factor gene NtWRKY65 enhances salt tolerance in tobacco (Nicotiana tabacum).

BACKGROUND: Salt stress severely inhibits plant growth, and the WRKY family transcription factors play important roles in salt stress resistance. In this study, we aimed to characterize the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance. RESULTS: This study characterized the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance using four NtWRKY65 overexpression lines. NtWRKY65 is localized to the nucleus, has transactivation activity, and is upregulated by NaCl treatment. Salinity treatment resulted in the overexpressing transgenic tobacco lines generating significantly longer roots, with larger leaf area, higher fresh weight, and greater chlorophyll content than those of wild type (WT) plants. Moreover, the overexpressing lines showed elevated antioxidant enzyme activity, reduced malondialdehyde content, and leaf electrolyte leakage. In addition, the Na+ content significantly decreased, and the K+/Na+ ratio was increased in the NtWRKY65 overexpression lines compared to those in the WT. These results suggest that NtWRKY65 overexpression enhances salinity tolerance in transgenic plants. RNA-Seq analysis of the NtWRKY65 overexpressing and WT plants revealed that NtWRKY65 might regulate the expression of genes involved in the salt stress response, including cell wall component metabolism, osmotic stress response, cellular oxidant detoxification, protein phosphorylation, and the auxin signaling pathway. These results were consistent with the morphological and physiological data. These findings indicate that NtWRKY65 overexpression confers enhanced salinity tolerance. CONCLUSIONS: Our results indicated that NtWRKY65 is a critical regulator of salinity tolerance in tobacco plants.

A retrospective investigation on clinical and radiographic outcomes of distal tibial fractures after intramedullary nailing using the lateral parapatellar extra-articular approach.

INTRODUCTION: According to reports, the modified extra-articular parapatellar approach allows the performance of tibial nailing in the semi-extended position without the concern of joint violation. However, there remains no special study that has provided a detailed assessment of the benefits and risks of this approach for treating distal tibial fractures (DTFs). The aim of this retrospective study was to investigate the clinical and radiological outcomes of patients with DTFs after intramedullary nailing using a lateral parapatellar extra-articular (LPE) approach in comparison to using the suprapatellar (SP) and transpatellar (TP) approaches. METHODS: Data were collected from 99 patients with a minimum follow-up period of 12 months. Comparisons were conducted between the groups regarding the number of intraoperative fluoroscopies, complications, knee pain, knee range of motion (ROM), the Lysholm Knee Scale (LKS), the Olerud-Molander Ankle Score (OMAS) and radiological findings. RESULTS: The demographic characteristics were comparable between the groups. Fewer intraoperative fluoroscopies were performed in the LPE (27.47 ± 4.98) and SP (26.03 ± 5.12) groups than in the TP group (30.20 ± 7.42; P<0.001). When compared with the other two approaches, the LPE approach was associated with less knee pain (P<0.001) and better knee ROM (P<0.001) at one week postoperative. No significant intergroup differences were detected in the incidence of complications, LKS scores (P = 0.687) and OMAS (P = 0.926). Radiological findings demonstrated that postoperative tibial alignment (P = 0.853), the time of bony union and rate of non-union were similar between the groups. CONCLUSION: The LPE approach can serve as a safe and effective option for tibial nailing, as it offers favourable outcomes in knee pain relief and knee ROM in the early postoperative period and is equivalent to the other two approaches in terms of the incidence of complications, fracture healing, functional recovery and postoperative alignment for patients with DTFs.

Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus.

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Towards an actionable One Health approach.

BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

Analysis of the clinical profile and treatment efficiency of hyperlipidemic acute pancreatitis.

BACKGROUND: The incidence of hyperlipidemic acute pancreatitis (HLAP) has been increasing annually. However, population-based morbidity assessments need to be updated. Early, rapid, and effective lipid-lowering may minimize pancreatic injury and improve clinical prognosis. It is essential to choose the proper treatment. However, treatment options for HLAP are controversial, and there is no uniform treatment protocol. METHODS: In this retrospective study, 127 patients with hyperlipidemic severe acute pancreatitis (HL-SAP) were registered from January 2018 to December 2022 at the General Hospital of Ningxia Medical University. Medical and radiological records of hospitalized patients were collected to determine clinical features, severity, complications, mortality, recurrence rate, and treatment. Risk factors for HL-SAP were analyzed using multifactorial logistic regression. A propensity score matching method was used to compare the clinical outcomes of standard and plasma exchange therapies. RESULTS: In this research, the prevalence of HLAP increased about 1.6 times, and the prevalence of HL-SAP was 50.60%. HL-SAP occurs most often in people between the ages of 30 and 39. Amylase exceeded 110 U/L in 84.3% of patients and 330 U/L in only 47.2%. 83.5% of HL-SAP patients had fatty livers and high body mass index (BMI). A total of 48.0% of patients experienced organ failure, ICU treatment (55.1%), recurrence (33.1%), and death (21.3%). Between the hyperlipidemic group and the biliary group in terms of age, gender, BMI, fatty liver, pleural effusion, abdominal constriction syndrome (ACS), multiple organ dysfunction syndrome (MODS), length of hospital, medical costs, morbidity and mortality, triglyceride, cholesterol, creatinine, blood glucose, D-dimer, amylase, albumin, lactate dehydrogenase, serum phosphorus, serum calcium, oxygenation index, and recurrence rate were statistically significant (P < 0.05). High BMI (P = 0.0038, odds ratio (OR) = 1.336, 95%CI: 0.99-1.804), high C-reactive protein (CRP) (P = 0.022, OR = 1.011, 95%CI: 1.003-1.019), low calcium (P = 0.003, OR = 0.016, 95%CI. 0.001-0.239), low albumin (P = 0.012, OR = 0.045, 95%CI: -0.062-0.192), and high D-dimer (P = 0.041, OR = 0.619, 95%CI: 0.053-2.510) were risk factors for HL-SAP, according to multifactorial logistic regression analysis. Adjusted for propensity score matching (PSM), Serum triglyceride (TG) was significantly lower in both the standard treatment (P < 0.001) and plasma exchange (P < 0.001) groups at 48 h compared with the initial test after the attack. Clearance (83.20% ± 0.0% vs. 84.4% ± 0.0%, P = 0.531), length of hospital stay (19.9 ± 4.9 vs. 19.8 ± 11.1, P = 0.092), and death (26.3% vs. 23.6%, P = 0.791) showed no difference between the two groups. However, the difference in medical costs(P = 0.039)between the two groups was statistically significant. CONCLUSION: The incidence of HLAP exhibited a significant increase, remarkable severity, recurrent trend, and mortality. High BMI, high CRP, low calcium, low albumin, and high D-dimer are risk factors for HL-SAP. Compared with standardized treatment, plasma exchange does not improve the prognosis of HL-SAP patients, and standardized treatment is equally effective, safe, and low-cost in early treatment.

Identification of a cis-element for long glandular trichome-specific gene expression, which is targeted by a HD-ZIP IV protein.

Glandular trichomes are epidermal outgrowths that secret a variety of secondary metabolites, which not only help plants adapt to environmental stresses but also have important commercial value in fragrances, pharmaceuticals, and pesticides. In Nicotiana tabacum, it has been confirmed that a B-type cyclin, CycB2, negatively regulates the formation of long glandular trichomes (LGTs). This study aimed to identify the upstream regulatory gene involved in LGT formation by screening LGT-specific cis-elements within the NtCycB2 promoter. Using GUS as a reporter gene, the tissue-driven ability of NtCycB2 promoter showed that NtCycB2 promoter could drive GUS expression specifically in LGTs. Function analysis of a series of successive 5' truncations and synthetic segments of the NtCycB2 promoter indicated that the 87-bp region from -1221 to -1134 of the NtCycB2 promoter was required for gene expression in LGTs, and the L1-element (5'-AAAATTAATAAGAG-3') located in the 87-bp region contributed to the gene expression in the stalk of LGTs. Further Y1H and LUC assays confirmed that this L1-element exclusively binds to a HD-Zip IV protein, NtHD13. Gene function analysis revealed that NtHD13 positively controlled LGT formation, as overexpression of NtHD13 resulted in a high number of LGTs, whereas knockout of NtHD13 led to a decrease in LGTs. These findings demonstrate that NtHD13 can bind to an L1-element within the NtCycB2 promoter to regulate LGT formation.

Transcriptome disclosure of hormones inducing stigma exsertion in Nicotiana tabacum by corolla shortening.

BACKGROUND: Stigma exsertion is an essential agricultural trait that can promote cross-pollination to improve hybrid seed production efficiency. However, the molecular mechanism controlling stigma exsertion remains unknown. RESULTS: In this study, the Nicotiana tabacum cv. K326 and its two homonuclear-heteroplasmic lines, MSK326 (male-sterile) and MSK326SE (male-sterile and stigma exserted), were used to investigate the mechanism of tobacco stigma exsertion. A comparison of the flowers between the three lines showed that the stigma exsertion of MSK326SE was mainly due to corolla shortening. Therefore, the corollas of the three lines were sampled and presented for RNA-seq analysis, which found 338 candidate genes that may cause corolla shortening. These genes were equally expressed in K326 and MSK326, but differentially expressed in MSK326SE. Among these 338 genes, 15 were involved in hormone synthesis or signal transduction pathways. Consistently, the content of auxin, dihydrozeatin, gibberellin, and jasmonic acid was significantly decreased in the MSK326SE corolla, whereas abscisic acid levels were significantly increased. Additionally, seven genes involved in cell division, cell cycle, or cell expansion were identified. Protein-protein interaction network analysis identified 45 nodes and 79 protein interactions, and the largest module contained 20 nodes and 52 protein interactions, mainly involved in the hormone signal transduction and pathogen defensive pathways. Furthermore, a putative hub gene coding a serine/threonine-protein kinase was identified for the network. CONCLUSIONS: Our results suggest that hormones may play a key role in regulating tobacco stigma exsertion induced by corolla shortening.

Inhibition of lysyl oxidase by pharmacological intervention and genetic manipulation alleviates epilepsy-associated cognitive disorder.

Epilepsy-associated cognitive disorder (ECD), a prevalent comorbidity in epilepsy patients, has so far uncharacterized etiological origins. Our prior work revealed that lysyl oxidase (Lox) acted as a novel contributor of ferroptosis, a recently discovered cell death mode in the regulation of brain function. However, the role of Lox-mediated ferroptosis in ECD remains unknown. ECD mouse model was established 2 months later following a single injection of kainic acid (KA) for. After chronic treatment with KA, mice were treated with different doses (30 mg/kg, 100 mg/kg and 300 mg/kg) of Lox inhibitor BAPN. Additionally, hippocampal-specific Lox knockout mice was also constructed and employed to validate the role of Lox in ECD. Cognitive functions were assessed using novel object recognition test (NOR) and Morris water maze test (MWM). Protein expression of phosphorylated cAMP-response element binding (CREB), a well-known molecular marker for evaluation of cognitive performance, was also detected by Western blot. The protein distribution of Lox was analyzed by immunofluorescence. In KA-induced ECD mouse model, ferroptosis process was activated according to upregulation of 4-HNE protein and a previously discovered ferroptosis in our group, namely, Lox was remarkably increased. Pharmacological inhibition of Lox by BAPN at the dose of 100 mg/kg significantly increased the discrimination index following NOR test and decreased escape latency as well as augmented passing times within 60 s following MWM test in ECD mouse model. Additionally, deficiency of Lox in hippocampus also led to pronounced improvement of deficits in ECD model. These findings indicate that the ferroptosis regulatory factor, Lox, is activated in ECD. Ablation of Lox by either pharmacological intervention or genetic manipulation ameliorates the impairment in ECD mouse model, which suggest that Lox serves as a promising therapeutic target for treating ECD in clinic.

In Vitro Comparative Analysis of the Effect and Structure-Based Influencing Factors of Flavonols on Lipid Accumulation.

Flavonols represented by quercetin have been widely reported to have biological activities of regulating lipid metabolism. However, the differences in flavonols with different structures in lipid-lowering activity and the influencing factors remain unclear. In this study, the stability, transmembrane uptake ratio, and lipid metabolism regulation activities of 12 flavonol compounds in the 3T3-L1 cell model were systematically compared. The results showed that kaempferide had the highest cellular uptake ratio and the most potent inhibitory effect on adipogenesis at a dosing concentration of 20 µM, followed by isorhamnetin and kaempferol. They inhibited TG accumulation by more than 65% and downregulated the expression of PPARγ and SREBP1c by more than 60%. The other four aglycones, including quercetin, did not exhibit significant activity due to the structural instability in the cell culture medium. Meanwhile, five quercetin glucosides were quite stable but showed a low uptake ratio that no obvious activity was observed. Correlation analysis also showed that for 11 compounds except galangin, the activity was positively correlated with the cellular uptake ratio (p < 0.05, r = 0.6349). These findings may provide a valuable idea and insight for exploring the structure-based activity of flavonoids at the cellular level.

Optimizing the algae-bacteria biofilm reactor for imidacloprid wastewater treatment: An evaluation of hydraulic retention times for enhanced efficiency and energy savings.

Recent observations have highlighted the rapidly growing prevalence of emerging contaminants such as Imidacloprid (IMI) within our environment. These insecticidal pollutants, coexisting with more traditional contaminants, have become predominant in aquatic systems, posing risks to both human and ecological well-being. Among the various wastewater treatment approaches tested, biofilm reactors are currently gaining prominence. In this study, we employed an Algae-Bacteria Biofilm Reactor (ABBR) to concurrently address both conventional and emergent contaminants, specifically IMI, over an extended timeframe. Following a 60-day assessment, the ABBR consistently demonstrated removal efficiencies exceeding 85% for total dissolved nitrogen, ammonia nitrogen, and total dissolved phosphorus, and also achieved removal efficacy for the soluble chemical oxygen demand (sCOD). Despite the removal efficiency of IMI (with initial concentration is 1.0 mg/L) in ABBR showed a gradual decline over the extended period, it remained consistently effective over 50% due to the microalgae-mediated free radical reactions, indicating the ABBR's sustained efficiency in long-duration operations. Additionally, applying some non-conventional modifications, like aeration removal and reducing light exposure, demonstrated minimal impact on the reactor's pollutant removal efficiencies, achieving comparable results to the control group (which utilized aeration with a 14:10 light/dark ratio), 0.92 kW h/L/d of electricity can be saved economically, which accentuated the potential for energy conservation. An in-depth analysis of the treated effluents from the ABBRs, using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique, uncovered four potential transformation pathways for IMI. Overall, our findings suggest that these optimized processes did not influence the transformation products of IMI, thereby reaffirming the viability of our proposed optimization.

Main effects and interactions of multiple key factors related to thermal perception.

The real indoor environment involves the comprehensive interaction of multiple factors, and human subjective responses to different factors are influenced by various aspects such as physics, physiology, and psychology. The relative significance of various factors influencing different types of human subjective thermal perception, as well as the extent of their interactions, remains somewhat unclear. This investigation, leveraging the "Chinese Thermal Comfort Dataset," analyzed the integrated impact of basic thermal perception factors-temperature, humidity, air speed, as well as clothing insulation and metabolic rate-on subjective thermal perception. The findings underscored the definitive role of air temperature as the primary determinant of thermal sensation, with the impact of other factors generally remaining below 15 % of temperature. Nonetheless, the sensitivity of thermal sensation to temperature is significantly affected by other factors, demonstrating a significant interaction between temperature and different factors in influencing temperature sensation. Additionally, it was observed that significant differences (p < 0.001) in thermal comfort levels existed even at the same thermal sensation. For instance, in the state of thermal neutrality, occupants with relatively higher clothing insulation reported higher thermal comfort level (d = 0.40, p < 0.001) during the cooling season but lower thermal comfort level (d = 0.54, P < 0.001) during the heating season. Consequently, it can be deduced that when comprehensively considering the impact of multiple factors, evaluating the environment solely based on thermal sensation or thermal neutrality may prove insufficient.

Improving the Storage Stability of Soy Protein Isolate through Annealing.

This study investigated the effect of annealing treatment on the stability of soy protein isolate (SPI) during storage. Different SPI samples with varying denaturation levels were subjected to varying annealing temperatures and durations before being stored at 37 °C for 12 weeks to assess their stability. Our findings revealed that annealing at 65 °C for 30 min significantly mitigated protein deterioration, improving the stability of highly denatured proteins during storage. Surface hydrophobicity and endogenous fluorescence analyses indicated that this annealing condition induced protein structure unfolding, an initial increase in SPI hydrophobicity, and a blue shift in the maximum absorption wavelength (λmax). The slowest increase in hydrophobicity occurred during storage, along with a red shift in the maximum absorption wavelength by the 12th week. These results suggest that annealing treatment holds promise for mitigating the issue of reduced SPI stability during storage.

Bone marrow-inspired hydrogel/graphene composite scaffolds to support in vitro expansion of hematopoietic stem cells.

Hematopoietic stem cell (HSC) expansion offers a key strategy to address the source limitation and donor shortages of HSCs for the treatment of various blood disorders. Specific remodeling of the complex bone marrow microenvironment that contributes to efficient in vitro expansion of HSCs remains challenging. Here, inspired by the regions with different stiffness levels in the bone marrow niche, a three dimensional (3D) bone marrow-mimicking composite scaffold created based on gelatin-hyaluronic acid (Gel-HA) hydrogels and graphene foams (GFs) was engineered to support the in vitro expansion of HSCs. The composite scaffold was prepared by forming a photo-cross-linked Gel-HA hydrogel surrounding the GF. The "soft" Gel-HA hydrogel and "stiff" GF replicate the structure and stiffness of the vascular niche and endosteal niche in the bone marrow, respectively. Furthermore, HSCs cultured in the Gel-HA/GF scaffold proliferated well and retained the CD34+CD38- immunophenotype and pluripotency, suggesting that the Gel-HA/GF composite scaffold supported the in vitro expansion of HSCs, maintaining the primitive phenotype and the ability to differentiate into functional blood cells. Thus, the hydrogel/graphene composite scaffold offers a means of facilitating HSC expansion through structurally and mechanically mimicking bone marrow niches, demonstrating great promise for HSC transplantation.

Synergistic inhibition against heterocyclic amines in beef patties: Caused by carbonyl-trapping and toxicity-reducing of amino acid combinations.

The inhibitory effects of amino acids and their combinations on the formation of heterocyclic amines were investigated in this study. The great potential in the inhibition of HAs was observed in amino acid combinations compared with that of single agents. At a mass ratio of 1:1, a His-Pro combination achieved a maximum inhibitory rate of 80 %, and the total HAs content decreased to 4.70 ± 0.18 ng/g relative to the control (24.49 ± 2.18 ng/g). However, the inhibitory rate of triple combinations showed no obvious increase compared with the binary combinations. Benzaldehyde, phenylacetaldehyde, methylglyoxal, and glyoxal were positively correlated with HAs formation, and His-Pro combination (1:4) led to a significant reduction of benzaldehyde and phenylacetaldehyde at scavenging rates of 79 % and 92 %. Thus, the synergistic inhibition was achieved by simultaneously scavenging these aldehyde intermediates, and other inhibitory target, such as competition with precursors and elimination of final products can serve as supporting factors. These results provide a new perspective for approaches to enhance the suppression of HAs and control the formation of flavor compounds.

Programmable Photoswitchable Microcapsules Enable Precise and Tailored Drug Delivery from Microfluidics.

The development of precision personalized medicine poses a significant need for the next generation of advanced diagnostic and therapeutic technologies, and one of the key challenges is the development of highly time-, space-, and dose-controllable drug delivery systems that respond to the complex physiopathology of patient populations. In response to this challenge, an increasing number of stimuli-responsive smart materials are integrated into biomaterial systems for precise targeted drug delivery. Among them, responsive microcapsules prepared by droplet microfluidics have received much attention. In this study, we present a UV-visible light cycling mediated photoswitchable microcapsule (PMC) with dynamic permeability-switching capability for precise and tailored drug release. The PMCs were fabricated using a programmable pulsed aerodynamic printing (PPAP) technique, encapsulating an aqueous core containing magnetic nanoparticles and the drug doxorubicin (DOX) within a poly(lactic-co-glycolic acid) (PLGA) composite shell modified by PEG-b-PSPA. Selective irradiation of PMCs with ultraviolet (UV) or visible light (Vis) allows for high-precision time-, space-, and dose-controlled release of the therapeutic agent. An experimentally validated theoretical model was developed to describe the drug release pattern, holding promise for future customized programmable drug release applications. The therapeutic efficacy and value of patternable cancer cell treatment activated by UV radiation is demonstrated by our experimental results. After in vitro transcatheter arterial chemoembolization (TACE), PMCs can be removed by external magnetic fields to mitigate potential side effects. Our findings demonstrate that PMCs have the potential to integrate embolization, on-demand drug delivery, magnetic actuation, and imaging properties, highlighting their immense potential for tailored drug delivery and embolic therapy.

Energy preservation for skeletal muscles: Shenqi Fuzheng injection prevents tissue wasting and restores bioenergetic profiles in a mouse model of chemotherapy-induced cachexia.

BACKGROUND: Energy deficiency is the characteristic of chemotherapy-induced cachexia (CIC) which is manifested by muscle wasting. glycolysis, tricarboxylic acid (TCA) cycle, and lipid metabolism are central to muscle bioenergy production, which is vulnerable to chemotherapy during cancer treatment. Recent investigations have spotlighted the potential of Shenqi Fuzheng injection (SQ), a Chinese proprietary medicine comprising Radix Codonopsis and Radix Astragali, in alleviating CIC. However, the specific effects of SQ on muscle energy metabolism remains less explored. PURPOSE AND METHODS: Here, we integrated transcriptomics, spatial metabolomics, gas chromatography-mass spectrometry targeted quantitative analysis, and transmission electron microscopy techniques, combined with Seahorse live-cell metabolic analysis to reveal the changes in genes and pathways related to energy metabolism in the CIC model and SQ's protective effects at molecular and functional levels. RESULTS: Our data showed that chemotherapeutic agents caused glycolysis imbalance, which further leads to metabolic derangements of TCA cycle intermediates. SQ maintained glycolysis balance by facilitating pyruvate fluxing to mitochondria for more efficient bioenergy production, which involved a dual effect on promoting functions of mitochondrial pyruvate dehydrogenase complexes and inhibiting lactate dehydrogenase for lactate production. As a result of the sustained pyruvate level achieved by SQ administration, glycolysis balance was maintained, which further led to the preservation of mitochondrial integrity and function of electron transport chain, thereby, ensuring the normal operation of the TCA cycle and the proper synthesis of adenosine triphosphate (ATP). The above results were further validated using the Seahorse live-cell assay. CONCLUSION: In conclusion, our study highlights SQ as a promising strategy for CIC management, emphasizing its ability to harmonize the homeostasis of the muscle bioenergetic profile. Beyond its therapeutic implications, this study also offers a novel perspective for the development of innovative treatments in the realm of herbal medicine.

PRL2 regulates neutrophil extracellular trap formation which contributes to severe malaria and acute lung injury.

Excessive host immune responses contribute to severe malaria with high mortality. Here, we show that PRL2 in innate immune cells is highly related to experimental malaria disease progression, especially the development of murine severe malaria. In the absence of PRL2 in myeloid cells, Plasmodium berghei infection results in augmented lung injury, leading to significantly increased mortality. Intravital imaging revealed greater neutrophilic inflammation and NET formation in the lungs of PRL2 myeloid conditional knockout mice. Depletion of neutrophils prior to the onset of severe disease protected mice from NETs associated lung injury, and eliminated the difference between WT and PRL2 CKO mice. PRL2 regulates neutrophil activation and NET accumulation via the Rac-ROS pathway, thus contributing to NETs associated ALI. Hydroxychloroquine, an inhibitor of PRL2 degradation alleviates NETs associated tissue damage in vivo. Our findings suggest that PRL2 serves as an indicator of progression to severe malaria and ALI. In addition, our study indicated the importance of PRL2 in NET formation and tissue injury. It might open a promising path for adjunctive treatment of NET-associated disease.

Synovial microenvironment-influenced mast cells promote the progression of rheumatoid arthritis.

Mast cells are phenotypically and functionally heterogeneous, and their state is possibly controlled by local microenvironment. Therefore, specific analyses are needed to understand whether mast cells function as powerful participants or dispensable bystanders in specific diseases. Here, we show that degranulation of mast cells in inflammatory synovial tissues of patients with rheumatoid arthritis (RA) is induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), and the expression of MHC class II and costimulatory molecules on mast cells are upregulated. Collagen-induced arthritis mice treated with a combination of anti-IL-17A and cromolyn sodium, a mast cell membrane stabilizer, show significantly reduced clinical severity and decreased bone erosion. The findings of the present study suggest that synovial microenvironment-influenced mast cells contribute to disease progression and may provide a further mast cell-targeting therapy for RA.

A General and Convenient Peptide Self-Assembling Mechanism for Developing Supramolecular Versatile Nanomaterials Based on The Biosynthetic Hybrid Amyloid-Resilin Protein.

Self-assembling peptides are valuable building blocks to fabricate supramolecular biomaterials, which have broad applications from biomedicine to biotechnology. However, limited choices to induce different globular proteins into hydrogels hinder these designs. Here, an easy-to-implement and tunable self-assembling strategy, which employs Ure2 amyloidogenic peptide, are described to induce any target proteins to assemble into supramolecular hydrogels alone or in combination with notable compositional control. Furthermore, the collective effect of nanoscale interactions among amyloid nanofibrils and partially disordered elastomeric polypeptides are investigated. This led to many useful macroscopic material properties simultaneously emerging from one pure protein material, i.e. strong adhesion to any substrates under wet conditions, rapidly self--assembling into robust and porous hydrogels, adaptation to remodeling processes, strongly promoting cell adhesion, proliferation and differentiation. Moreover, he demonstrated this supramolecular material's robust performance in vitro and vivo for tissue engineering, cosmetic and hemostasis applications and exhibited superior performance compared to corresponding commercial counterparts. To the best of his knowledge, few pure protein-based materials could meet such seemingly mutually exclusive properties simultaneously. Such versatility renders this novel supramolecular nanomaterial as next-generation functional protein-based materials, and he demonstrated the sequence level modulation of structural order and disorder as an untapped principle to design new proteins.

Intermittent fasting and Alzheimer's disease-Targeting ketone bodies as a potential strategy for brain energy rescue.

Alzheimer's disease (AD) lacks effective clinical treatments. As the disease progresses, the cerebral glucose hypometabolism that appears in the preclinical phase of AD gradually worsens, leading to increasingly severe brain energy disorders. This review analyzes the brain energy deficit in AD and its etiology, brain energy rescue strategies based on ketone intervention, the effects and mechanisms of IF, the differences in efficacy between IF and ketogenic diet and the duality of IF. The evidence suggests that brain energy deficits lead to the development and progression of AD pathology. IF, which improves brain energy impairments by promoting ketone metabolism, thus has good therapeutic potential for AD.