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Background: Tracheal adenoid cystic carcinoma (ACC) is a slow growing yet aggressive malignancy with high rates of local recurrence as well as distant metastasis. Tracheal ACC exhibit a low mutation burden along with high mutational diversity, and generally do not respond well to chemotherapeutics., Methods: We present a rare case of primary tracheal ACC initially presenting with nonspecific cervicalgia and globus sensation that was ultimately treated with tracheal resection followed by chemoradiation. Immune profiling of intratumoral T-cell receptor (TCR) repertoire was subsequently performed using single cell RNA sequencing (scRNAseq)., Results: We describe a rare case of primary tracheal adenoid cystic carcinoma highlighting several management principles as well as providing new insights into intratumor T cell populations., Conclusions: Primary tracheal ACC is most commonly treated with surgical resection followed by adjuvant therapy. Further characterization of the tumor immune microenvironment is necessary to better understand ACC disease biology and to identify potential therapeutic targets., (© 2024 Wiley Periodicals LLC.)

Background: Protein acetylation is an important post-translational modification (PTM) that widely exists in organisms. As a reversible PTM, acetylation modification can regulate the function of proteins with high efficiency. In the previous study, the acetylation sites of silkworm proteins were identified on a large scale by nano-HPLC/MS/MS (nanoscale high performance liquid chromatography-tandem secondary mass spectrometry), and a total of 11 acetylation sites were discovered on Bombyx mori nutrient-storage protein SP3 (BmSP3). The purpose of this study was to investigate the effect of acetylation level on BmSP3., Methods and Results: In this study, the acetylation of BmSP3 was further verified by immunoprecipitation (IP) and Western blotting. Then, it was confirmed that acetylation could up-regulate the expression of BmSP3 by improving its protein stability in BmN cells. Co-IP and RNAi experiments showed acetyltransferase BmCBP could bind to BmSP3 and catalyze its acetylation modification, then regulate the expression of BmSP3. Furthermore, the knock-down of BmCBP could improve the ubiquitination level of BmSP3. Both acetylation and ubiquitination occur on the side chain of lysine residues, therefore, we speculated that the acetylation of BmSP3 catalyzed by BmCBP could competitively inhibit its ubiquitination modification and improve its protein stability by inhibiting ubiquitin-mediated proteasome degradation pathway, and thereby increase the expression and intracellular accumulation., Conclusions: BmCBP catalyzes the acetylation of BmSP3 and may improve the stability of BmSP3 by competitive ubiquitination. This conclusion provides a new functional basis for the extensive involvement of acetylation in the regulation of nutrient storage and utilization in silkworm, Bombyx mori., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

There is a lack of research on how Tibetan kefir grains fermentation alters the physicochemical properties and biological activity of Lycium barbarum pulp polysaccharides, despite some reports that fermentation can affect the structure and activity of plant polysaccharides. This study demonstrated that, through fermentation, the molecular weight of polysaccharides decreased from 25.33 to 15.11 kg/mol while the contents of total sugar and uronic acid increased by 19.11% and 40.38%, respectively. Furthermore, after fermentation, the polysaccharides exhibited an uneven and rough surface along with a reduced number of branched chains and triple helix structures. Tibetan kefir grains fermentation enhanced the antioxidant activity of polysaccharides, which may be attributed to an increase in arabinose, galactose, and uronic acid content and a decrease in polysaccharide molecular weight. This research offers an alternative viewpoint on the potential application of Tibetan kefir grains-fermented Lycium barbarum pulp polysaccharides in functional foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This prospective cohort study, conducted at the Fenglin Community Health Service Center (FCHC) in Xuhui District, Shanghai, aimed to investigate the impact of maternal psychological status on offspring neurodevelopment., Methods: A total of 430 mother-child pairs were included, with pregnant women enrolled between February 18, 2020, and April 19, 2021. Face-to-face interviews and electronic data collection on demographic characteristics, health conditions and medical history were employed at various stages of pregnancy and postpartum. Maternal depression and anxiety were assessed using the PHQ-9 and GAD-7 scales, while offspring neurodevelopment was measured at six months using the Ages and Stages Questionnaire 3rd Edition (ASQ-3). In statistical analyses, group-based trajectory modeling (GBTM) was employed to identify the latent groups for maternal psychological trajectories, including depression and anxiety, and logistic regression was used to explore associations between maternal psychological trajectories and offspring neurodevelopment, adjusting for potential confounders., Results: Five latent trajectory groups were identified for both depression and anxiety, exhibiting distinct patterns over time. Results indicated that maternal psychological trajectories were associated with various domains of offspring neurodevelopment, including communication, problem-solving, personal-social, and gross motor skills. Specifically, mothers in trajectory groups characterized by the highest level of depression or anxiety showed increased odds of offspring neurodevelopmental delays compared to reference groups., Conclusion: Our findings underscore the importance of maternal mental health during the perinatal period and highlight the potential implications for offspring neurodevelopment. Further research is warranted to elucidate underlying mechanisms and inform targeted interventions to support maternal mental well-being and optimize offspring outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Multidrug resistance (MDR) Klebsiella pneumoniae (K. pneumoniae) is a major emerging threat to human health, and leads to very high mortality rate. The effectiveness of colistin, the last resort against MDR Gram-negative bacteria, is significantly compromised due to the widespread presence of plasmid- or chromosome-mediated resistance genes. In this study, o-cymen-5-ol has been found to greatly restore colistin sensitivity in MDR K. pneumoniae. Importantly, this compound does not impact bacterial viability, induce resistance, or cause any noticeable cell toxicity. Various routes disclosed the potential mechanism of o-cymen-5-ol potentiating colistin activity against MDR K. pneumoniae. These include inhibiting the activity of plasmid-mediated mobile colistin resistance gene (mcr-1), accelerating lipopolysaccharide (LPS) - mediated membrane damage, and promoting the ATP-binding cassette (ABC) transporter pathway. To enhance the administration and bioavailability of o-cymen-5-ol, a nanoemulsion has been designed, which significantly improves the loading efficiency and solubility of o-cymen-5-ol, resulting in antimicrobial potentiation of colistin against K. pneumoniae infection. This study has revealed a new understanding of the o-cymen-5-ol nanoemulsion as a means to enhance the effectiveness of colistin against resistant factors. The finding also suggests that o-cymen-5-ol nanoemulsion could be a promising approach in the development of potential treatments for multidrug-resistant Gram-negative bacterial infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Given expanding studies in epidemiology and disease-oriented human studies offering hundreds of associations between the human "ome" and disease, prioritizing molecules relevant to disease mechanisms among this growing breadth is important. Here, we link the circulating proteome to human heart failure (HF) propensity (via echocardiographic phenotyping and clinical outcomes) across the lifespan, demonstrating key pathways of fibrosis, inflammation, metabolism, and hypertrophy. We observe a broad array of genes encoding proteins linked to HF phenotypes and outcomes in clinical populations dynamically expressed at a transcriptional level in human myocardium during HF and cardiac recovery (several in a cell-specific fashion). Many identified targets do not have wide precedent in large-scale genomic discovery or human studies, highlighting the complementary roles for proteomic and tissue transcriptomic discovery to focus epidemiological targets to those relevant in human myocardium for further interrogation., Competing Interests: Declaration of interests S.G.D. is a consultant for Abbott, and S.G.D. and K.J.L. have industry research support from Novartis. R.V.S. has served as a consultant for Amgen, Cytokinetics, and Thryv Therapeutics (with options ownership in Thryv). R.V.S. is a co-inventor on a patent for ex-RNA signatures of cardiac remodeling and a pending patent on proteomic signatures of fitness and lung and liver diseases. R.V.S. also has stock options with Thryv Therapeutics. A.S.P. is a co-inventor on a pending patent for proteomic signatures of fitness, lung, and liver diseases. K.A. does ad hoc consulting for Tegus and Guidepoint and serves on a DSMB for Fortrea. M.N. has received speaking honoraria from Cytokinetics. K.J.L. serves as a consultant for Medtronic, Implicit Biosciences, Kiniksa Pharmaceuticals, and Cytokinetics. K.J.L. receives grant support from Amgen, Novartis, Kiniksa Pharmaceuticals, and Implicit Biosciences. S.D. is a co-founder and has equity in Thryv therapeutics and Switch Therapeutics. S.D. has received grant support from Abbot Laboratories and Bristol Myers Squib. S.D. is a co-inventor on a patent on tissue-specific EV-RNAs. R.K. has received personal fees from GSK, Astrazeneca, Boehringer Ingelheim, and CVS Caremark. S.J.S. has received consulting fees from 35Pharma, Abbott, Alleviant, AstraZeneca, Amgen, Aria CV, Axon Therapies, BaroPace, Bayer, Boehringer-Ingelheim, Boston Scientific, BridgeBio, Bristol Myers Squibb, Corvia, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, eMyosound, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, ReCor, Regeneron, Rivus, SalubriusBio, Sardocor, Shifamed, Tectonic, Tenax, Tenaya, Ulink, and Ultromics. J.M.A. was employed by Amgen. J.W. reports consulting/scientific advisory board for Abiomed, Abbott, Astra Zeneca, Boehringer Ingelheim, and Cytokinetics within the last 24 months., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Foxtail millet and sourdough are used to make foxtail millet sourdough steamed bread to improve the flavor and taste. Compared with the conventional freeze-thaw treatment (CFT), the effect of magnetic field-assisted freeze-thaw treatment (MFT) on the storage quality of foxtail millet sourdough and steamed bread is explored. The results showed that compared with CFT, MFT shortened the phase transition time of dough; decreased the water loss rate, the water mobility, and the freezable water content; increased the fermentation volume; stabilized the rheological properties; and minimized the damage of freezing and thawing to the secondary structure and microstructure of the gluten. In addition, an analysis of the specific volume, texture, surface color, and texture structure showed that MFT was beneficial to slowing the deterioration of the steamed bread texture. Finally, MFT effectively inhibited the growth and recrystallization of ice crystals during freezing and thawing, improving the quality of millet dough and steamed bread., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: TANK-binding kinase 1 (TBK1) is a pivotal mediator of innate immunity, activated by receptors such as mitochondrial antiviral signaling protein (MAVS), stimulator of interferon genes (STING), and TIR-domain-containing adaptor inducing interferon-β (TRIF). It modulates immune responses by exerting influence on the type I interferons (IFN-Is) signaling and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, Over the past few years, TBK1 multifaceted role in both immune and inflammatory responses is increasingly recognized., Methods and Results: This review aims to scrutinize how TBK1 operates within the NF-κB pathway and the interferon regulatory transcription factor 3 (IRF3)-dependent IFN-I pathways, highlighting the kinases and other molecules involved in these processes. This analysis reveals the distinctive characteristics of TBK1's involvement in these pathways. Furthermore, it has been observed that the role of TBK1 in exerting anti-inflammatory or pro-inflammatory effects is contingent upon varying pathological conditions, indicating a multifaceted role in immune regulation., Discussion: TBK1's evolving role in various diseases and the potential of TBK1 inhibitors as therapeutic agents are explored. Targeting TBK1 may provide new strategies for treating inflammatory disorders and autoimmune diseases associated with IFN-Is, warranting further investigation.

In this study, the effects of the Cd-resistant and pyoverdine-producing strain Pseudomonas umsongensis CR14 on Cd stabilization and the mechanisms were investigated. Compared with the control, CR14 markedly reduced the Cd concentration in a Cd-containing solution. The genes pvdA, 4498, 4499, and pchF, which are associated with pyoverdine production, were identified in CR14. Subsequently, CR14 and the CR14ΔpvdA, CR14Δ4498, CR14Δ4499, and CR14ΔpchF mutants were characterized for their effects on Cd stabilization in solution. After 72 h of incubation, the CR14ΔpchF and CR14ΔpvdA mutants significantly decreased Cd concentrations compared with CR14. Notably, the CR14ΔpvdA mutant showed a greater impact on Cd stabilization than the other mutants. Compared with CR14, this mutant brought a lower Cd concentration in the solution, with higher levels of cell surface-adsorbed and intracellular accumulated Cd, content of lipopolysaccharide (LPS), expression of the LPS-producing genes lptD and lpxL, and cell surface particles. Additionally, compared with CR14, the CR14ΔpvdA mutant demonstrated increased interactions between the hydroxyl, carboxyl, amino, or ether groups and Cd. These results suggest that the CR14ΔpvdA mutant immobilized Cd by increasing LPS production and cell surface particle numbers, upregulating the expression of LPS-producing genes, and increasing cell surface adsorption and intracellular accumulation in Cd-polluted solutions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Non-genetic mechanisms have recently emerged as important drivers of anticancer drug resistance. Among these, the drug tolerant persister (DTP) cell phenotype is attracting more and more attention and giving a predominant non-genetic role in cancer therapy resistance. The DTP phenotype is characterized by a quiescent or slow-cell-cycle reversible state of the cancer cell subpopulation and inert specialization to stimuli, which tolerates anticancer drug exposure to some extent through the interaction of multiple underlying mechanisms and recovering growth and proliferation after drug withdrawal, ultimately leading to treatment resistance and cancer recurrence. Therefore, targeting DTP cells is anticipated to provide new treatment opportunities for cancer patients, although our current knowledge of these DTP cells in treatment resistance remains limited. In this review, we provide a comprehensive overview of the formation characteristics and underlying drug tolerant mechanisms of DTP cells, investigate the potential drugs for DTP (including preclinical drugs, novel use for old drugs, and natural products) based on different medicine models, and discuss the necessity and feasibility of anti-DTP therapy, related application forms, and future issues that will need to be addressed to advance this emerging field towards clinical applications. Nonetheless, understanding the novel functions of DTP cells may enable us to develop new more effective anticancer therapy and improve clinical outcomes for cancer patients., (© 2024. The Author(s).)

Phytoremediation coupled with agroproduction (PCA) model contributes to sustainable agriculture and environmental management. This study investigated the impact of continuous cropping early/late season rice (RR) and Sedum alfredii-rice rotation (SR) on soil physical and chemical properties, as well as their relationships with soil microbial community. In 2022, SR treatment significantly increased pH value and organic matter content by 7 % and 17 %, respectively, compared to the levels in 2020, while RR treatment showed no change. RR treatment resulted in a significant decrease in soil concentrations of Ca, Mg, and K by 18.42 %, 29.01 %, and 7.77 %, respectively. Furthermore, SR treatment saw reductions of 29.62 % in total Cd and 38.30 % in DTPA extractable Cd in the soil. Over the two years, both treatments notably influenced the diversity, structure, and network of the rhizosphere bacterial and fungal communities, which are crucial for nutrient cycling and plant health. Notably, SR treatment exhibited a more complex network compared to RR, suggesting a greater impact on the interconnected systems. Therefore, these findings highlight the potential of Sedum rotation system to rehabilitate contaminated soils while supporting agricultural practices, which is essential for food security and environmental sustainability. This research direction holds promise for future exploration and application in the fields of phytoremediation and agroecology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In this study, the Pb-resistant Ensifer adhaerens strain S24, which contains quorum sensing (QS) systems responsible for N-acyl homoserine lactone (AHL) production, was investigated for QS system-mediated Pb stabilization and the underlying mechanisms. Whole-genome sequence analysis revealed the QS SinI/R and TraI/R systems in strain S24. Subsequently, strains S24 and the S24∆sinI/R, S24∆traI/R, S24∆traI/R/sinR, and S24∆sinI/R-traI/R/sinR mutants were constructed and compared for QS SinI/SinR-TraI/TraR system-mediated Pb stabilization in the solution and the mechanisms involved. After 5 days of incubation, strain S24 significantly decreased the Pb concentration in the Pb-contaminated solution compared with the mutants. The S24∆sinI/R-traI/R/sinR mutant exhibited reduced Pb stabilization and AHL activity than the other mutants. The S24∆sinI/R-traI/R/sinR mutant had significantly greater Pb concentrations in the solution and lower cell surface-adsorbed and extracellular precipitated Pb (PbS) contents as well as lower expression of H 2 S-producing genes of metC and sseA than did strain S24. Furthermore, the S24∆sinI/R-traI/R/sinR mutant displayed reduced interactions between the hydroxyl, amino, carboxyl, and ether groups and Pb, compared with strain S24. These findings implied the vital role of the SinI/SinR-TraI/TraR systems in strain S24 for Pb stabilization through enhanced cell surface adsorption and extracellular precipitation in Pb-polluted aquatic environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Medicago sativa polysaccharides (MSPs) are beneficial compounds extracted from Medicago sativa L. that exhibit multiple medicinal activities. However, little is known about their hypoglycemic effects. In this study, MSP-II-a, a neutral polysaccharide with an Mw of 4.3 × 104 Da, was isolated and purified from M. sativa L. Monosaccharide composition analysis determined that MSP-II-a was composed of arabinose, glucose, galactose, mannose, rhamnose, and xylose in a molar ratio of 2.1:4.0:1.1:0.4:1.4:1.1. Structural characterization of MSP-II was performed using a combination of methylation analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. The results showed that MSP-II-a was mainly comprised of 1,4-p-Glc, 1,3,4-Rha, and 1,3-p-Gal glycosidic linkages, revealing a mesh-like texture with irregular blade shapes. In vitro assays demonstrated that MSP-II-a, at concentrations of 200 and 400 μg/mL, promoted glucose uptake in insulin-resistant 3T3-L1 adipocytes. In vivo studies have shown that MSP-II-a significantly alleviates insulin resistance by reducing fasting blood glucose levels and increasing hepatic glycogen synthesis in HFD/STZ-induced diabetic mice. These findings revealed that MSP-II-a is a promising source of bioactive polysaccharides with potential hypoglycemic activity., (© 2024 Wiley‐VCH GmbH.)

Fullerene (C 60 ) crystals have attracted considerable attention in the field of optoelectronic devices owing to their excellent performance as n-type semiconductor material. However, a challenge still remains unbeaten as to the continuous crystallization of non-solvated C 60 single-crystal films with high coverage and uniform alignment using low-cost solution techniques. Here, a facile bar coating method is used to prepare ribbon-shaped non-solvated C 60 crystals with a large area (up to centimeters) and high coverage (>95%) by precisely controlling the crystallization process from specific solvents. Benefiting from the non-solvated crystalline structure, well-distributed thickness, uniform morphological alignment, and crystallographic orientation, organic field-effect transistors fabricated from the C 60 single-crystal films exhibit a high average electron mobility of 2.28 cm 2  V -1 s -1 , along with the coefficient of variance (CV) as small as 13.6%. This efficient manufacturing method will lay a strong foundation for C 60 single-crystal films to fit into the future high-performance integrated optoelectronic application., (© 2024 Wiley‐VCH GmbH.)

Objective: The objective of this study was to identify the transcriptional landscape of insulin resistance (IR) in subcutaneous adipose tissue (SAT) in humans across the spectrum of obesity., Methods: We used SAT RNA sequencing in 220 individuals with metabolic phenotyping., Results: We identified a 35-gene signature with high predictive accuracy for homeostatic model of IR that was expressed across a variety of non-immune cell populations. We observed primarily "protective" IR associations for adipocyte transcripts and "deleterious" associations for macrophage transcripts, as well as a high concordance between SAT and visceral adipose tissue (VAT). Multiple SAT genes exhibited dynamic expression 5 years after weight loss surgery and with insulin stimulation. Using available expression quantitative trait loci in SAT and/or VAT, we demonstrated similar genetic effect sizes of SAT and VAT on type 2 diabetes and BMI., Conclusions: SAT is conventionally viewed as a metabolic buffer for lipid deposition during positive energy balance, whereas VAT is viewed as a dominant contributor to and prime mediator of IR and cardiometabolic disease risk. Our results implicate a dynamic transcriptional architecture of IR that resides in both immune and non-immune populations in SAT and is shared with VAT, nuancing the current VAT-centric concept of IR in humans., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Self-assembled Eu-dipeptide (tryptophan-phenylalanine) microparticles with multi-emission fluorescence was prepared and modified with a single-stranded DNA corresponding to the sulfamethazine (SMZ) adapter (Eu-PMPs@cDNA). Aptamer-functionalized magnetic Fe 3 O 4 (MNPs@aptamer) was used to specifically bind the target SMZ. Using Eu-PMPs@cDNA as fluorescent signal probe and MNPs@aptamer as catcher, a noncompetitive fluorescence sensing strategy was developed for determination of SMZ with good sensitivity, accuracy, selectivity, and stability. Under the optimized conditions, fluorescence increases linearly in the 0-20 ng/mL SMZ concentration range, and the detection limit is 0.014 ng/mL. The fluorescence sensing method was applied to analysis of water and fish muscle samples, and recoveries ranged from 81.78 to 119.46 % with relative standard deviations below 4.2 %. This study offered a reliable and sensitive fluorescence sensing strategy for SMZ determination in food samples, which owns great potential for wide-ranging application in harmful compounds assay by simply changing the type of aptamer and its complementary single-stranded DNA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Findings regarding the relationship between sarcopenia and lymphoma have been inconsistent across studies. This study investigated the association between sarcopenia and lymphoma. We systematically searched the Embase, Science Direct, Cochrane Library, and PubMed databases from inception to 31 March 2024 to identify relevant studies. Two researchers independently extracted and evaluated studies that met inclusion and exclusion criteria. Twenty-six studies with 3659 participants were included. Sarcopenic lymphoma patients had poor overall survival (OS) (HR = 1.88; 95% CI: 1.47-2.41; p  < 0.001). The heterogeneity was high (I 2 =80%). However, the result of the Egger test indicated a significant publication bias ( p  < 0.001). After employing the trim and fill method to adjust for this bias, the HR of OS became non-significant ( p  > 0.05). The progression-free survival (PFS) was worse in sarcopenic patients (HR = 1.77; 95% CI: 1.37-2.29; p  < 0.001; I 2 =70%). There was no significant publication bias ( p  > 0.05). In the subgroup analyses, sarcopenia was a negative predictor of OS in lymphoma patients who undergo hematopoietic cell transplantation (HCT) (HR  = 1.61;95% CI: 1.19-2.18; I 2 =30%). Male lymphoma patients with sarcopenia had a significantly worse OS (HR = 2.29; 95% CI:1.24-4.24; p  = 0.009). Among patients with primary central nervous system lymphoma (PCNSL), those with sarcopenia defined by temporal muscle thickness (TMT) exhibited significantly worse OS (HR = 2.20; 95% CI:1.04-4.65; p  = 0.039; I 2 =68%). Sarcopenia is associated with worse PFS in lymphoma patients. Subgroup analyses indicate that sarcopenia is a negative predictor of OS after HCT, and male lymphoma patients who suffer from sarcopenia have higher mortality. Sarcopenia defined by TMT is also a negative predictor of OS for patients with PCNSL.

Background: Polymyxin E is widely recognized as a last resort for treating multidrug-resistant gram-negative bacteria. Unfortunately, the effectiveness of polymyxin E is significantly reduced when treating life-threatening bacterial infections due to plasmid-mediated polymyxin E resistance. The synergistic effect of applying a polymyxin E adjuvant is a promising strategy for overcoming the growing threat of antibiotic-resistant pathogens., Purpose: To evaluate the synergistic effect of fisetin and polymyxin E on S. typhimurium infections in vivo and further elucidate the underlying mechanism of this effect., Methods: The effect of combining fisetin and polymyxin E to treat mobilized colistin resistance-1-positive (MCR-1-positive) gram-negative bacteria in vitro was examined using various methods, such as checkerboard assays, growth curves and time‒kill curves. To elucidate the mechanism by which fisetin affects MCR-1, we employed ultraviolet (UV) absorption spectroscopy, thin layer chromatography (TLC), and western blot analysis to investigate its effect at the protein level. Subsequently, molecular dynamics simulations (MDS) and metabolomics analysis were utilized to determine the site of interaction between fisetin and MCR-1 as well as the potential pathways and mechanisms involved. A new nanoemulsion of fisetin was produced using high-pressure homogenization, and its stability was tested. Finally, two animal models of S. typhimurium HYM2 infection were established to evaluate the synergistic effect of polymyxin E and fisetin in vivo., Results: Our study revealed that fisetin exhibited a synergistic effect when combined with polymyxin E against MCR-1-positive S. typhimurium. The TLC results demonstrated that fisetin could inhibit the phosphoethanolamine (PEA) transfer of the MCR-1 protein, thereby restoring the activity of polymyxin E in strains against MCR-1. The MDS analysis indicated robust and immediate binding between fisetin and the MCR-1 protein, with both hydrophobic and polar effects playing significant roles in determining the binding energy of the former. Metabolomic studies demonstrated that the addition of fisetin significantly modulated bacterial metabolites. Moreover, it effectively inhibited the activity of ABC transporters in bacteria, thereby mitigating bacterial drug resistance and enhancing the therapeutic efficacy of polymyxin E. Furthermore, in mouse and chick models of infection, intragastric administration of the fisetin nanoemulsion together with polymyxin E resulted in significant therapeutic benefits, including increased survival rates, reduced bacterial colonization, and decreased levels of inflammatory factors., Conclusion: Fisetin, an MCR-1 inhibitor and a promising synergistic partner of polymyxin E, has significant potential for clinical application in the treatment of S. typhimurium infections, particularly those resulting extensively from drug-resistant MCR-1-positive strains., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: The morphology of proximal humeral fractures (PHFs) is complex, and the fixation and selection of implants need to be guided by the fracture type and classification, which requires an accurate understanding of the fracture line. This study had three purposes. 1) Define and analyze the fracture lines and morphological features of all types PHFs by three-dimensional (3D) mapping technology. 2) Determine the osteotomy position of the biomechanical model of the PHFs according to the fracture heat map. 3) Based on the analysis of the pathological morphology and distribution of a large number of consecutive cases of PHFs, propose a novel classification of PHFs. Methods: We retrospectively collected 220 cases of PHFs and generated a 3D fracture map and heat map based on computed tomography (CT) imaging. Through analysis of the fracture morphology of the 220 PHFs, a novel classification was proposed. The primary criterion for staging was the continuity between the humeral head and the greater tuberosity and lesser tuberosity, and the secondary criterion was the relationship between the humeral head segment and the humeral shaft. Results: The fracture line was primarily found around the metaphyseal zone of region of the surgical neck, with the most extensive distribution being below the larger tuberosity and on the posterior medial side of the epiphysis. We suggest that the osteotomy gap should be immediately (approximately 5-10 mm) below the lower edge of the articular surface. The most common type of fracture was type I3 (33 cases, 15.0%), followed by type IV3 fracture (23 cases, 10.4%), and type III2 fracture (22 cases, 10.0%). Interobserver and intraobserver reliability analysis for the fracture classification revealed a k value (95% confidence interval) of 0.639 (0.57-0.71) and 0.841, P < 0.01, respectively. Conclusion: In this study, the fracture line and morphological characteristics of PHFs were clarified in detail by 3D mapping technique. In addition, a new classification method was proposed by analysis of the morphological characteristics of 220 PHFs, A two-part fracture model for PHFs is also proposed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Zhang, Ding, Zhang, Sheng and Piao.)

Background: Cardiac allograft vasculopathy (CAV), a diffuse thickening of the intima of the coronary arteries and microvasculature, is the leading cause of late graft failure and mortality after heart transplantation (HT). Diagnosis involves invasive coronary angiography, which carries substantial risk, and minimally-invasive approaches to CAV diagnosis are urgently needed. Using single-cell RNA-sequencing in peripheral blood mononuclear cells (PBMCs), we sought to identify cell-specific gene expression profiles in CAV., Methods: Whole blood was collected from 22 HT recipients with angiographically-confirmed CAV and 18 HT recipients without CAV. PBMCs were isolated and subjected to single-cell RNA-sequencing using a 10X Genomics microfluidic platform. Downstream analyses focused on differential expression of genes, cell compositional changes, and T cell receptor repertoire analyses., Results: Across 40 PBMC samples, we isolated 134,984 cells spanning 8 major clusters and 31 subclusters of cell types. Compositional analyses showed subtle, but significant increases in CD4+ T central memory cells, and CD14+ and CD16+ monocytes in high-grade CAV (CAV-2 and CAV-3) as compared to low-grade or absent CAV. After adjusting for age, gender, and prednisone use, 745 genes were differentially expressed in a cell-specific manner in high-grade CAV. Weighted gene co-expression network analyses showed enrichment for putative pathways involved in inflammation and angiogenesis. There were no significant differences in T cell clonality or diversity with increasing CAV severity., Conclusions: Unbiased whole transcriptomic analyses at single-cell resolution identify unique, cell-specific gene expression patterns in CAV, suggesting the potential utility of peripheral gene expression biomarkers in diagnosing CAV.

Soft pneumatic actuation is widely used in wearable devices, soft robots, artificial muscles, and surgery machines. However, generating high-pressure gases in a soft, controllable, and portable way remains a substantial challenge. Here, a class of programmable chemical reactions that can be used to controllably generate gases with a maximum pressure output of nearly 6 MPa is reported. It is proposed to realize the programmability of the chemical reaction process using thermoelectric material with programmable electric current and employing preprogrammed reversible chemical reactants. The programmable chemical reactions as soft pneumatic actuation can be operated independently as miniature gas sources (∼20-100 g) or combined with arbitrary physical structures to make self-contained machines, capable of generating unprecedented pressures of nearly 6 MPa or forces of about 18 kN in a controllable, portable, and silent manner. Striking demonstrations of breaking a brick, a marble, and concrete blocks, raising a sightseeing car, and successful applications in artificial muscles and soft assistive wearables illustrate tremendous application prospects of soft pneumatic actuation via programmable chemical reactions. The study establishes a new paradigm toward ultrastrong soft pneumatic actuation., (© 2024 Wiley‐VCH GmbH.)

Background: Retroperitoneal lymphatic malformations (LMs) are rare. Currently, the treatment of retroperitoneal LMs remains challenging. This study aimed to examine the safety and efficacy of laparoscopic-assisted sclerotherapy for retroperitoneal LMs in pediatric patients., Methods: We retrospectively reviewed patients treated with laparoscopic-assisted sclerotherapy for retroperitoneal LMs in a single tertiary medical center between July 2020 and February 2023. Doxycycline was prepared into a solution with a concentration of 10 mg/ml for use in sclerotherapy. Demographic data, clinical features, details of management, and outcomes were collected and analyzed., Results: A total of six patients, comprising three males and three females, were identified. The LMs were categorized into four macrocystic and two mixed-cystic types. The mean age and weight were 52.2 months (range, 11-108 months) and 20 kg (range, 12.5-27.5 kg), respectively. Three patients presented with abdominal pain or distension, while the other three patients were asymptomatic. All six patients underwent a total of eight sclerotherapy sessions. Two patients experienced intra-cystic hemorrhage and required a second sclerotherapy session. Only one patient presented with vomiting after sclerotherapy, which resolved spontaneously. Five patients met the complete response criteria, and one patient met the effective criteria. The mean reduction in lesion size was 92.3% (range, 69.9%-99.6%). No further complications or recurrence were recorded during follow-up., Conclusion: Laparoscopic-assisted sclerotherapy is a safe and effective approach for treating retroperitoneal LMs. This technique is applicable for both macrocystic and mixed-cystic retroperitoneal LMs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Shi, Lv, Xu, Liu, Sheng, Ren and Chen.)

Proximal humerus fractures (PHFs) are common in the elderly and usually involve defects in the medial column.The current standard for medial column reconstruction is a lateral locking plate (LLP) in combination with either an intramedullary fibula support or an autogenous fibula graft. However, autogenous fibula graft can lead to additional trauma for patients and allogeneic fibular graft can increase patients' economic burden and pose risks of infection and disease transmission. The primary objective of this study was to introduce and assess a novel "Sandwich" fixation technique and compare its biomechanical properties to the traditional fixation methods for PHFs. In this study, we established finite element models of two different internal fixation methods: LLP-intramedullary reconstruction plate with bone cement (LLP-IRPBC) and LLP-intramedullary fibula segment (LLP-IFS). The biomechanical properties of the two fixation methods were evaluated by applying axial, adduction, abduction, torsional loads and screw extraction tests to the models. These FEA results were subsequently validated through a series of biomechanical experiments. Under various loading conditions such as axial, adduction, abduction, and rotation, the LLP-IRPBC group consistently demonstrated higher structural stiffness and less displacement compared to the LLP-IFS group, regardless of whether the bone was in a normal (Nor) or osteoporotic (Ost) state. Under axial, abduction and torsional loads, the maximum stress on LLPs of LLP-IRPBC group was lower than that of LLP-IFS group, while under adduction load, the maximum stress on LLPs of LLP-IRPBC group was higher than that of LLP-IFS group under Ost condition, and almost the same under Nor condition. The screw-pulling force in the LLP-IRPBC group was 1.85 times greater than that of the LLP-IFS group in Nor conditions and 1.36 times greater in Ost conditions. Importantly, the results of the biomechanical experiments closely mirrored those obtained through FEA, confirming the accuracy and reliability of FEA. The novel "Sandwich" fixation technique appears to offer stable medial support and rotational stability while significantly enhancing the strength of the fixation screws. This innovative approach represents a promising strategy for clinical treatment of PHFs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lv, Zhang, Qv, Sheng, Zhang and Piao.)

Tea plant ( Camellia sinensis [ L .]) is one of the most important crops in China, and tea branch is an important agronomic trait that determines the yield of tea plant. In previous work focused on GWAS that detecting GWAS signals related to plant architecture through whole genome re-sequencing of ancient tea plants, a gene locus TEA 029928 significantly related to plant type was found. Sequence alignment results showed that this gene belonged to the F-box family. We named it CsBRC . CsBRC-GFP fusion proteins were mainly localized in the plasma membrane. By comparing the phenotypes of CsBRC transgenic tobacco and WT tobacco, it was found that the number of branches of transgenic tobacco was significantly higher than that of wild-type tobacco. Through RNA-seq analysis, it was found that CsBRC affects the branching development of plants by regulating the expression of genes related to brassinosteroid synthesis pathway in plants. In addition, overexpression of CsBRC in rice could increase tiller number, grain length and width, and 1,000-grain weight., Competing Interests: The authors declare that they have no competing interest., (© 2024 The Author(s). Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

Purpose: To present the process from acute Posner-Schlossman syndrome (PSS) relapse to remission under 2% ganciclovir (GCV), corticosteroids and anti-glaucoma agents on 323 patients., Methods: A retrospective study enrolling 323 PSS patients. Demographics and ophthalmic examination results were generated. Patients were treated with GCV, corticosteroids and anti-glaucoma agents andfollowed up every 2-6 weeks., Results: Patients were divided into the GCV monotherapy ( N  = 65, 20.12%), GCV and corticosteroids (G+C, N  = 106) and GCV, corticosteroid and IOP-lowering drugs (G+C+L, N  = 152) group. The G+C+L group had the highest intraocular pressure (IOP, 26.33 ± 10.26 mmHg, P  < 0.001) and largest cup-to-disc ratio (0.58 ± 0.19, P  < 0.05). After treatment, IOP of three groups dropped to similar level. Ninety-nine (30.65%) patients were corticosteroid-dependent whose daily corticosteroid consumption decreased after using GCV (from 2.23 ± 1.02 to 0.97 ± 0.98 drops/day)., Conclusion: 2% GCV solutions worked effectively on PSS relapse with corticosteroids and anti-glaucoma agents. In patients suspected of CMV infection, proper GCV could reduce the chance of corticosteroid dependence.

Purpose: This study focused on the prevalence, unique features, and required treatment of steroid-dependent Posner-Schlossman syndrome (SD-PSS), and analyzed the outcome of 2% Ganciclovir and gradual decrement steroid combination therapy in SD-PSS patients., Methods: Retrospective comparative and interventional study. SD-PSS was defined as PSS patients with continuous steroid use for over 3 months and relapsed within 2 weeks after steroid withdrawal or tapered dosage. Totally 74 SD-PSS eyes were compared with 78 randomly chosen non-steroid dependent PSS eyes. SD-PSS patients who underwent 2% GCV and gradual decrement steroid therapy with at least two follow-ups ( n  = 50) were analyzed for the treatment outcome., Results: The prevalence of SD-PSS is 26.87% (97/361) in our PSS patients. SD-PSS patients demonstrated significantly younger onset age, longer disease course, higher intraocular pressure (IOP), and higher degree of iris depigmentation at the first visit. They required significantly more IOP-lowering medication and stronger steroid after the first visit. Our 2% GCV and gradual decrement steroid therapy helped 66% (33/50) SD-PSS patients with steroid withdrawal (median stable time: 13 weeks) and another 32% (16/50) SD-PSS managed to lower the dose or strength of topical steroid. Steroid-induced ocular hypertension happened in 5.26% (19/361) of the PSS patients., Conclusion: Young onset age, high IOP, and high iris depigmentation level during acute stage are indicators of steroid dependency in PSS patients. SD-PSS patients require more medical surveillance. Two percent ganciclovir and gradual decrement steroid combination therapy help with steroid withdrawal and minimize steroid use.

Objectives: Recent immunologic study of the adaptive immune repertoire in the subglottic airway demonstrated high-frequency T cell clones that do not overlap between individuals. However, the anatomic distribution and antigenic target of the T cell repertoire in the proximal airway mucosa remain unresolved., Methods: Single-cell RNA sequencing of matched scar and unaffected mucosa from idiopathic subglottic stenosis patients (iSGS, n = 32) was performed and compared with airway mucosa from healthy controls (n = 10). T cell receptor (TCR) sequences were interrogated via similarity network analysis to explore antigenic targets using the published algorithm: Grouping of Lymphocyte Interactions by Paratope Hotspots (GLIPH2)., Results: The mucosal T cell repertoire in healthy control airways consisted of highly expressed T cell clones conserved across anatomic subsites (trachea, bronchi, bronchioles, and lung). In iSGS, high-frequency clones were equally represented in both scar and adjacent non-scar tissue. Significant differences in repertoire structure between iSGS scar and unaffected mucosa was observed, driven by unique low-frequency clones. GLIPH2 results suggest low-frequency clones share targets between multiple iSGS patients., Conclusion: Healthy airway mucosa has a highly conserved T cell repertoire across multiple anatomic subsites. Similarly, iSGS patients have highly expressed T cell clones present in both scar and unaffected mucosa. iSGS airway scar possesses an abundance of less highly expanded clones with predicted antigen targets shared between patients. Interrogation of these shared motifs suggests abundant adaptive immunity to viral targets in iSGS airway scar. These results provide insight into disease pathogenesis and illuminate new treatment strategies in iSGS., Level of Evidence: NA Laryngoscope, 134:3245-3252, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Weifeng Zou,1 Xiaoqian Wang,2 Wei Hong,3 Fang He,4 Jinxing Hu,1 Qing Sheng,1 Tao Zhu,1 Pixin Ran5 1State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, Guangdong, People’s Republic of China; 2State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 3GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 4The Research Center of Experiment Medicine, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 5State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Pixin RanState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Yuexiu District, Guangzhou, Guangdong 510120, People’s Republic of China, Tel +86 13922765811Email pxran@gzhmu.edu.cnBackground and Purpose: Recently, fine particulate matter (PM2.5) was identified as the main exposure risk for COPD, and inflammation is central to the development of COPD. In this study, we investigated whether PM2.5 can induce the secretion of interleukin-6 (IL-6), IL-8 and IL-1β in human bronchial epithelial cells (HBECs) in vitro via the wingless-related integration site 5A (Wnt5a)/receptor tyrosine kinase-like orphan receptor 2 (Ror2) signaling.Methods: The expression of Wnt5a and Ror2 was assessed by immunohistochemistry in motor vehicle exhaust (MVE)-induced Sprague-Dawley rats. HBECs were transfected with small interfering RNA (siRNA) targeting Wnt5a or Ror2 and subsequently stimulated with PM2.5.The secretion of IL-6, IL-8 and IL-1β was assessed by ELISAs, and the expression of Wnt5a/Ror2 signaling were assessed by RT-PCR and Western blotting.Results: Both Wnt5a and Ror2 protein were increased in the lung of MVE-induced rats. HBECs exposed to PM2.5 for 24 h significantly upregulated Wnt5a and Ror2 expression and subsequently promoted the nuclear translocation of NF-κB, which increased the production of IL-1β, IL-6 and IL-8. Wnt5a siRNA prevented these outcomes. Wnt5a antagonist (BOX5) also prevented inflammatory effects. Furthermore, Ror2 siRNA blocked the NF-κB activity and inhibited the release of IL-6, IL-8 and IL-1β from PM2.5-exposed HBECs.Conclusion: PM2.5 induces the secretion of IL-6, IL-8 and IL-1β in HBECs via the Wnt5a/Ror2 signaling, demonstrating a novel mechanism for PM2.5-associated airway inflammation.Key words: COPD, PM2.5, Wnt5a/ROR2, inflammatory cytokines, HBECs

Andrographolide (Andro), a labdane diterpene, possesses anti-inflammatory properties and has been used to treat numerous inflammatory diseases. Novel findings revealed that Andro might be vital in regulating pain. However, the contribution of Andro to chronic inflammatory pain has yet to be determined, and its underlying mechanism of action remains unknown. In this study, we observed that Andro attenuated mechanical allodynia in inflammatory pain mice induced by injecting complete Freund's adjuvant (CFA) into the right hind paws. This analgesic effect of Andro is mainly dependent on its inhibition of microglial overactivation and the release of proinflammatory cytokines (TNF and IL-1β) in lumbar spinal cords of inflammatory pain model mice. More importantly, our data in vivo and in vitro revealed a negative role for Andro in regulating the TLR4/NF-κB signaling pathway, which might contribute to the inhibition of spinal microglial activation and proinflammatory cytokines production, and the improvement of paw withdrawal thresholds in a mouse model of chronic inflammatory pain evoked by CFA. We further found the potential interaction of Andro with TLR4/myeloid differentiation factor 2 heterodimer using molecular modeling, implying that TLR4 might be a potential target for Andro to exert an analgesic effect. Taken together, our findings demonstrated that the modulation of spinal microglial activation by Andro might be substantially conducive to managing chronic pain triggered by neuroinflammation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The coordinated rehabilitation of the upper limb is important for the recovery of the daily living abilities of stroke patients. However, the guidance of the joint coordination model is generally lacking in the current robot-assisted rehabilitation. Modular robots with soft joints can assist patients to perform coordinated training with safety and compliance. In this study, a novel coordinated path planning and impedance control method is proposed for the modular exoskeleton elbow–wrist rehabilitation robot driven by pneumatic artificial muscles (PAMs). A convolutional neural network-long short-term memory (CNN-LSTM) model is established to describe the coordination relationship of the upper limb joints, so as to generate adaptive trajectories conformed to the coordination laws. Guided by the planned trajectory, an impedance adjustment strategy is proposed to realize active training within a virtual coordinated tunnel to achieve the robot-assisted upper limb coordinated training. The experimental results showed that the CNN-LSTM hybrid neural network can effectively quantify the coordinated relationship between the upper limb joints, and the impedance control method ensures that the robotic assistance path is always in the virtual coordination tunnel, which can improve the movement coordination of the patient and enhance the rehabilitation effectiveness.