Label-free detection and profiling of individual solution-phase molecules.

Most chemistry and biology occurs in solution, in which conformational dynamics and complexation underlie behaviour and function. Single-molecule techniques1 are uniquely suited to resolving molecular diversity and new label-free approaches are reshaping the power of single-molecule measurements. A label-free single-molecule method2-16 capable of revealing details of molecular conformation in solution17,18 would allow a new microscopic perspective of unprecedented detail. Here we use the enhanced light-molecule interactions in high-finesse fibre-based Fabry-Pérot microcavities19-21 to detect individual biomolecules as small as 1.2 kDa, a ten-amino-acid peptide, with signal-to-noise ratios (SNRs) >100, even as the molecules are unlabelled and freely diffusing in solution. Our method delivers 2D intensity and temporal profiles, enabling the distinction of subpopulations in mixed samples. Notably, we observe a linear relationship between passage time and molecular radius, unlocking the potential to gather crucial information about diffusion and solution-phase conformation. Furthermore, mixtures of biomolecule isomers of the same molecular weight and composition but different conformation can also be resolved. Detection is based on the creation of a new molecular velocity filter window and a dynamic thermal priming mechanism that make use of the interplay between optical and thermal dynamics22,23 and Pound-Drever-Hall (PDH) cavity locking24 to reveal molecular motion even while suppressing environmental noise. New in vitro ways of revealing molecular conformation, diversity and dynamics can find broad potential for applications in the life and chemical sciences.

OpenFold: retraining AlphaFold2 yields new insights into its learning mechanisms and capacity for generalization.

AlphaFold2 revolutionized structural biology with the ability to predict protein structures with exceptionally high accuracy. Its implementation, however, lacks the code and data required to train new models. These are necessary to (1) tackle new tasks, like protein-ligand complex structure prediction, (2) investigate the process by which the model learns and (3) assess the model's capacity to generalize to unseen regions of fold space. Here we report OpenFold, a fast, memory efficient and trainable implementation of AlphaFold2. We train OpenFold from scratch, matching the accuracy of AlphaFold2. Having established parity, we find that OpenFold is remarkably robust at generalizing even when the size and diversity of its training set is deliberately limited, including near-complete elisions of classes of secondary structure elements. By analyzing intermediate structures produced during training, we also gain insights into the hierarchical manner in which OpenFold learns to fold. In sum, our studies demonstrate the power and utility of OpenFold, which we believe will prove to be a crucial resource for the protein modeling community.

Bergamot essential oil improves CUMS-induced depression-like behaviour in rats by protecting the plasticity of hippocampal neurons.

Bergamot essential oil (BEO) is an extract of the bergamot fruit with significant neuroprotective effect. This study was to investigate the effects and the underlying mechanism of BEO in mitigating depression. GC-MS were used to identify its constituents. Antidepressive properties of BEO were evaluated by sucrose preference test (SPT), force swimming test (FST) and open field test (OFT). Nissl staining was used to determine the number of Nissl bodies in hippocampus (HIPP) of rats. Changes in HIPP dendritic length and dendritic spine density were detected by Golgi-Cox staining. Immunohistochemistry and Western blot were used to detect the postsynaptic density protein-95 (PSD-95) and synaptophysin (SYP) in the HIPP of rats. The enzyme-linked immunosorbent assay was used to determine the 5-hydroxytryptamine (5-HT), insulin-like growth factor 1 (IGF-1) and interleukin-1ß (IL-1ß) in the HIPP, serum and cerebrospinal fluid (CSF) of rats. Inhaled BEO significantly improved depressive behaviour in chronic unpredictable mild stress (CUMS) rats. BEO increased Nissl bodies, dendritic length and spine density, PSD-95 and SYP protein in the HIPP. Additionally, BEO upregulated serum 5-HT, serum and CSF IGF-1, while downregulating serum IL-1ß. Collectively, inhaled BEO mitigates depression by protecting the plasticity of hippocampal neurons, hence, providing novel insights into treatment of depression.

Castration alters the ileum microbiota of Holstein bulls and promotes beef flavor compounds.

BACKGROUND: In the beef industry, bull calves are usually castrated to improve flavor and meat quality; however, this can reduce their growth and slaughter performance. The gut microbiota is known to exert a significant influence on growth and slaughter performance. However, there is a paucity of research investigating the impact of castration on gut microbiota composition and its subsequent effects on slaughter performance and meat flavor. RESULT: The objective of this study was to examine the processes via which castration hinders slaughter productivity and enhances meat quality. Bull and castrated calves were maintained under the same management conditions, and at slaughter, meat quality was assessed, and ileum and epithelial tissue samples were obtained. The research employed metagenomic sequencing and non-targeted metabolomics techniques to investigate the makeup of the microbiota and identify differential metabolites. The findings of this study revealed the Carcass weight and eye muscle area /carcass weight in the bull group were significantly higher than those in the steer group. There were no significant differences in the length, width, and crypt depth of the ileum villi between the two groups. A total of 53 flavor compounds were identified in the two groups of beef, of which 16 were significantly higher in the steer group than in the bull group, and 5 were significantly higher in the bull group than in the steer group. In addition, bacteria, Eukaryota, and virus species were significantly separated between the two groups. The lipid metabolism pathways of α-linolenic acid, linoleic acid, and unsaturated fatty acids were significantly enriched in the Steers group. Compared with the steer group, the organic system pathway is significantly enriched in the bull group. The study also found that five metabolites (LPC (0:0/20:3), LPC (20:3/0:0), LPE (0:0/22:5), LPE (22:5/0:0), D-Mannosamine), and three species (s_Cloning_vector_Hsp70_LexA-HP1, s_Bacteroides_Coprophilus_CAG: 333, and s_Clostridium_nexile-CAG: 348) interfere with each other and collectively have a positive impact on the flavor compounds of beef. CONCLUSIONS: These findings provide a basic understanding that under the same management conditions, castration does indeed reduce the slaughter performance of bulls and improve the flavor of beef. Microorganisms and metabolites contribute to these changes through interactions.

Evolving brain network dynamics in early childhood: Insights from modular graph metrics.

Modular dynamic graph theory metrics effectively capture the patterns of dynamic information interaction during human brain development. While existing research has employed modular algorithms to examine the overall impact of dynamic changes in community structure throughout development, there is a notable gap in understanding the cross-community dynamic changes within different functional networks during early childhood and their potential contributions to the efficiency of brain information transmission. This study seeks to address this gap by tracing the trajectories of cross-community structural changes within early childhood functional networks and modeling their contributions to information transmission efficiency. We analyzed 194 functional imaging scans from 83 children aged 2 to 8 years, who participated in passive viewing functional magnetic resonance imaging sessions. Utilizing sliding windows and modular algorithms, we evaluated three spatiotemporal metrics-temporal flexibility, spatiotemporal diversity, and within-community spatiotemporal diversity-and four centrality metrics: within-community degree centrality, eigenvector centrality, between-community degree centrality, and between-community eigenvector centrality. Mixed-effects linear models revealed significant age-related increases in the temporal flexibility of the default mode network (DMN), executive control network (ECN), and salience network (SN), indicating frequent adjustments in community structure within these networks during early childhood. Additionally, the spatiotemporal diversity of the SN also displayed significant age-related increases, highlighting its broad pattern of cross-community dynamic interactions. Conversely, within-community spatiotemporal diversity in the language network exhibited significant age-related decreases, reflecting the network's gradual functional specialization. Furthermore, our findings indicated significant age-related increases in between-community degree centrality across the DMN, ECN, SN, language network, and dorsal attention network, while between-community eigenvector centrality also increased significantly for the DMN, ECN, and SN. However, within-community eigenvector centrality remained stable across all functional networks during early childhood. These results suggest that while centrality of cross-community interactions in early childhood functional networks increases, centrality within communities remains stable. Finally, mediation analysis was conducted to explore the relationships between age, brain dynamic graph metrics, and both global and local efficiency based on community structure. The results indicated that the dynamic graph metrics of the SN primarily mediated the relationship between age and the decrease in global efficiency, while those of the DMN, language network, ECN, dorsal attention network, and SN primarily mediated the relationship between age and the increase in local efficiency. This pattern suggests a developmental trajectory in early childhood from global information integration to local information segregation, with the SN playing a pivotal role in this transformation. This study provides novel insights into the mechanisms by which early childhood brain functional development impacts information transmission efficiency through cross-community adjustments in functional networks.

Visible-Light-Activated Heteroaryl Azoswitches: Toward a More Colorful Future.

Azobenzenes (Ph-N═N-Ph) are known as the most widely studied molecular photoswitches, and the recent rise of azoheteroarenes (Het-N═N-Ph or Het-N═N-Het) offers great opportunities to advance this already mature field. A common limitation is that azo-switches generally require harmful UV light for activation, which hinders their application across various fields. Despite great efforts in developing visible-light azobenzenes over the past few decades, the potential of visible-light heteroaryl azoswitches remains largely unexplored. This Perspective summarizes the state-of-the-art advancements in visible-light heteroaryl azoswitches, covering molecular design strategies, the structure-property relationship, and potential applications. We highlight the distinctive advantages of azoheteroarenes over azobenzenes in the research and development of visible-light switches. Furthermore, we discuss the opportunities and challenges in this emerging field and propose potential solutions to address crucial issues such as spectral red-shift and thermal half-life. Through this Perspective paper, we aim to provide inspiration for further exploration in this field, in anticipation of the growing prosperity and bright future of visible-light azoheteroarene photoswitches.

Electron Divergence of Cuδ- and Pdδ+ in Cu3Pd Alloy-Based Heterojunctions Boosts Concerted C≡C Bond Binding and the Volmer Step for Alkynol Semihydrogenation.

Electrocatalytic semihydrogenation of alkynols presents a sustainable alternative to conventional thermal methodologies for the high-value production of alkenols. The design of efficient catalysts with superior catalytic and energy efficiency for semihydrogenation poses a significant challenge. Here, we present the application of an electron-divergent Cu3Pd alloy-based heterojunction in promoting the electrocatalytic semihydrogenation of alkynols to alkenols using water as the proton source. The tunable electron divergence of Cuδ- and Pdδ+, modulated by rectifying contact with nitrogen-rich carbons, enables the concerted binding of active H species from the Volmer step of water dissociation and the C≡C bond of alkynols on Pdδ+ sites. Simultaneously, the pronounced electron divergence of Cu3Pd facilitates the universal adsorption of OH species from the Volmer step and alkynols on the Cuδ- sites. The electron-divergent dual-center substantially boosts water dissociation and inhibition of completing hydrogen evolution to give a turnover frequency of 2412 h-1, outperforming the reported electrocatalysts' value of 7.3. Moreover, the continuous production of alkenols at industrial-related current density (-200 mA cm-2) over the efficient and durable Cu3Pd-based electrolyzer could achieve a cathodic energy efficiency of 45 mol kW·h-1, 1.7 times the bench-marked reactors, promising great potential for sustainable industrial synthesis.

Isolation of a Virulent Clostridium perfringens Strain from Elaphurus davidianus and Characterization by Whole-Genome Sequence Analysis.

Clostridium perfringens (C. perfringens) is an important veterinary pathogen and a noteworthy threat to human and animal health. Recently, there has been a significant rise in the number of moose fatalities caused by this rare, endemic species in China. Currently, there is an increasing trend in conducting whole-genome analysis of C. perfringens strains originating from pigs and chickens, whereas fewer studies have been undertaken on Elaphurus davidianus-originating strains at the whole-genome level. Our laboratory has identified and isolated five C. perfringens type A from affected Elaphurus davidianus. The current study identified the most potent strain of C. perfringens, which originated from Elaphurus davidianus, and sequenced its genome to reveal virulence genes and pathogenicity. Our findings show that strain CX1-4 exhibits the highest levels of phospholipase activity, hemolytic activity, and mouse toxicity compared to the other four isolated C. perfringens type A strains. The chromosome sequence length of the CX1-4 strain was found to be 3,355,389 bp by complete genome sequencing. The current study unveils the genomic characteristics of C. perfringens type A originating from Elaphurus davidianus. It provides a core foundation for further investigation regarding the prevention and treatment of such infectious diseases in Elaphurus davidianus.

Unraveling T cell exhaustion in the immune microenvironment of osteosarcoma via single-cell RNA transcriptome.

Osteosarcoma (OS) represents a profoundly invasive malignancy of the skeletal system. T cell exhaustion (Tex) is known to facilitate immunosuppression and tumor progression, but its role in OS remains unclear. In this study, single-cell RNA sequencing data was employed to identify exhausted T cells within the tumor immune microenvironment (TIME) of OS. We found that exhausted T cells exhibited substantial infiltration in OS samples. Pseudotime trajectory analysis revealed a progressive increase in the expression of various Tex marker genes, including PDCD1, CTLA4, LAG3, ENTPD1, and HAVCR2 in OS. GSVA showed that apoptosis, fatty acid metabolism, xenobiotic metabolism, and the interferon pathway were significantly activated in exhausted T cells in OS. Subsequently, a prognostic model was constructed using two Tex-specific genes, MYC and FCGR2B, which exhibited exceptional prognostic accuracy in two independent cohorts. Drug sensitivity analysis revealed that OS patients with a low Tex risk were responsive to Dasatinib and Pazopanib. Finally, immunohistochemistry verified that MYC and FCGR2B were significantly upregulated in OS tissues compared with adjacent tissues. This study investigates the role of Tex within the TIME of OS, and offers novel insights into the mechanisms underlying disease progression as well as the potential treatment strategies for OS.

Nanoencapsulated MgBu2@ZIF-67 to Construct High Loading Mg-Co@C Nanocomposites: Breaking Through the Barrier of Room Temperature Onset Dehydrogenation.

The synergies of nanoconfinement and catalysis is an effective strategy to improve the kinetic and thermodynamic properties of Mg-based materials. However, obtaining Mg-based materials with high loading, anti-aggregation, and containing nanocatalysts to achieve dehydrogenation at room temperature remains a huge challenge. Herein, a novel and universal preparation strategy for Mg-Co@C nanocomposites with 9.5 nm Mg nanoparticles and 9.4 nm Co nanocatalysts embedded in carbon scaffold is reported. The 9.3 nm MgBu2 nanosheets precipitated by solvent displacement are encapsulated in ZIF-67 to prepare MgBu2@ZIF-67 precursors, then removing excess MgBu2 on the precursor surface and pyrolysis to obtain Mg-Co@C. It is worth noting that the Mg loading rate of Mg-Co@C is as high as rare 69.7%. Excitingly, the Mg-Co@C begins to dehydrogenate at room temperature with saturate capacity of 5.1 wt.%. Meanwhile, its dehydrogenation activation energy (Ea(des) = 68.8 kJ mol-1) and enthalpy (ΔH(des) = 61.6 kJ mol-1) significantly decrease compared to bulk Mg. First principles calculations indicate that the hydrogen adsorption energy on the Mg2CoH5 surface is only -0.681 eV. This work provides a universally applicable novel method for the preparation of nanoscale Mg-based materials with various nanocatalysts added, and provides new ideas for Mg-based materials to achieve room temperature hydrogen storage.

Enhanced Charge Transfer in Quasi-2D Perovskite by Formamidinium Cation Gradient Incorporation for Efficient and Stable Solar Cells.

Quasi-2D perovskites have attracted much attention in perovskite photovoltaics due to their excellent stability. However, their photoelectric conversion efficiency (PCE) still lags 3D counterparts, particularly with high short-circuit current (JSC) loss. The quantum confinement effect is pointed out to be the sole reason, which introduces widened bandgap and poor exciton dissociation, and undermines the light capture and charge transport. Here, the gradient incorporation of formamidinium (FA) cations into quasi-2D perovskite is proposed to address this issue. It is observed that FA prefers to incorporate into the larger n value phases near the film surface compared to the smaller n value phases in the bulk, resulting in a narrow bandgap and gradient structure within the film. Through charge dynamic analysis using in situ light-dark Kelvin probe force microscopy and transient absorption spectroscopy, it is demonstrated that incorporating 10% FA significantly facilitates efficient charge transfer between low n-value phases in the bulk and high n-value nearby film surface, leading to reduced charge accumulation. Ultimately, the device based on (AA)2(MA0.9FA0.1)4Pb5I16, where AA represents n-amylamine renowned for its exceptional environmental stability as a bulky organic ligand, achieves an impressive power conversion efficiency (PCE) of 18.58% and demonstrates enhanced illumination and thermal stability.

Global level of methylation in the sea lamprey (jawless vertebrate) genome is intermediate between invertebrate and jawed vertebrate genomes.

In eukaryotes, cytosine methylation is a primary heritable epigenetic modification of the genome that regulates many cellular processes. In invertebrate, methylated cytosine generally located on specific genomic elements (e.g., gene bodies and silenced repetitive elements) to show a "mosaic" pattern. While in jawed vertebrate (teleost and tetrapod), highly methylated cytosine located genome-wide but only absence at regulatory regions (e.g., promoter and enhancer). Many studies imply that the evolution of DNA methylation reprogramming may have helped the transition from invertebrates to jawed vertebrates, but the detail remains largely elusive. In this study, we used the whole-genome bisulfite-sequencing technology to investigate the genome-wide methylation in three tissues (heart, muscle, and sperm) from the sea lamprey, an extant agnathan (jawless) vertebrate. Strikingly, we found that the methylation level of the sea lamprey is very similar to that in sea urchin (a deuterostome) and sea squirt (a chordate) invertebrates. In sum, the global pattern in sea lamprey is intermediate methylation level (around 30%), that is higher than methylation level in the genomes of pre-bilaterians and protostomes (1%-10%), but lower than methylation level appeared in jawed vertebrates (around 70%, teleost and tetrapod). We anticipate that, in addition to genetic dynamics such as genome duplications, epigenetic dynamics such as global methylation reprograming was also orchestrated toward the emergence and evolution of vertebrates.

Two transcription factors, RhERF005 and RhCCCH12, regulate rose resistance to Botrytis cinerea by modulating cytokinin levels.

Gray mold caused by the necrotrophic fungal pathogen Botrytis cinerea is one of the most destructive diseases in rose (Rosa spp.). Rose infection by B. cinerea leads to severe economic losses due to necrosis, tissue collapse, and rot. In rose, cytokinins (CKs) positively regulate a defense response to B. cinerea, but little is known about the underlying molecular mechanisms. Here, we characterized two ethylene/jasmonic acid-regulated transcription factors, RhEFR005 and RhCCCH12, that bind to the promoter region of PATHOGENESIS-RELATED 10.1 (RhPR10.1) and promote its transcription, leading to decreased susceptibility to B. cinerea. The RhEFR005/RhCCCH12-RhPR10.1 module regulated cytokinin content in rose, and the susceptibility of RhEFR005-, RhCCCH12-, and RhPR10.1-silenced rose petals can be rescued by exogenous CK. In summary, our results reveal that the RhERF005/RhCCCH12-RhPR10.1 module regulates the CK-induced defense response of rose to B. cinerea.

Transcription factors RhbZIP17 and RhWRKY30 enhance resistance to Botrytis cinerea by increasing lignin content in rose petals.

The petals of ornamental plants such as roses (Rosa spp.) are the most economically important organs. This delicate, short-lived plant tissue is highly susceptible to pathogens, in large part because the walls of petal cells are typically thinner and more flexible compared with leaf cells, allowing the petals to fold and bend without breaking. The cell wall is a dynamic structure that rapidly alters its composition in response to pathogen infection, thereby reinforcing its stability and boosting plant resistance against diseases. However, little is known about how dynamic changes in the cell wall contribute to resistance to Botrytis cinerea in rose petals. Here, we show that the B. cinerea-induced transcription factor RhbZIP17 is required for the defense response of rose petals. RhbZIP17 is associated with phenylpropanoid biosynthesis and binds to the promoter of the lignin biosynthesis gene RhCAD1, activating its expression. Lignin content showed a significant increase under gray mold infection compared with the control. RhCAD1 functions in the metabolic regulation of lignin production and, consequently, disease resistance, as revealed by transient silencing and overexpression in rose petals. The WRKY transcription factor RhWRKY30 is also required to activate RhCAD1 expression and enhance resistance against B. cinerea. We propose that RhbZIP17 and RhWRKY30 increase lignin biosynthesis, improve the resistance of rose petals to B. cinerea, and regulate RhCAD1 expression.

Exploring the intricacies of Pasteurella multocida dynamics in high-altitude livestock and its consequences for bovine health: A personal exploration of the yak paradox.

Pasturella multocida (P. multocida), a gram-negative bacterium, has long been a focus of interest in animal health because of its capacity to cause different infections, including hemorrhagic septicemia. Yaks, primarily found in high-altitude environments, are among the several livestock animals affected by these bacteria. Yaks are essential to the socioeconomic life of the people who depend on them since they are adapted to the cold and hypoxic conditions of highland environments. Nevertheless, these terrains exhibit a greater incidence of P. multocida despite the severe environmental complications. This predominance has been linked to the possible attenuation of the yak's immunological responses in such circumstances and the evolution of some bacterial strains to favor survival in the respiratory passages of the animals. Moreover, these particular strains threaten other cattle populations that interact with yaks, which might result in unanticipated outbreaks in areas previously thought to be low risk. Considering these findings, designing and executing preventative and control strategies suited explicitly for these distinct biological environments is imperative. Through such strategies, yaks' health will be guaranteed, and a larger bovine population will be safeguarded against unanticipated epidemics. The current review provides thorough insights that were previously dispersed among several investigations. Its distinct method of connecting the ecology of yaks with the dynamics of infection offers substantial background information for further studies and livestock management plans.

Topological Photonic Alloy.

We present the new concept of photonic alloy as a nonperiodic topological material. By mixing nonmagnetized and magnetized rods in a nonperiodic 2D photonic crystal configuration, we realized photonic alloys in the microwave regime. Our experimental findings reveal that the photonic alloy sustains nonreciprocal chiral edge states even at very low concentration of magnetized rods. The nontrivial topology and the associated edge states of these nonperiodic systems can be characterized by the winding of the reflection phase. Our results indicate that the threshold concentrations for the investigated system within the first nontrivial band gap to exhibit topological behavior approach zero in the thermodynamic limit for substitutional alloys, while the threshold remains nonzero for interstitial alloys. At low concentration, the system exhibits an inhomogeneous structure characterized by isolated patches of nonpercolating magnetic domains that are spaced far apart within a topologically trivial photonic crystal. Surprisingly, the system manifests chiral edge states despite a local breakdown of time-reversal symmetry rather than a global one. Photonic alloys represent a new category of disordered topological materials, offering exciting opportunities for exploring topological materials with adjustable gaps.

Lattice QCD Calculation of Electroweak Box Contributions to Superallowed Nuclear and Neutron Beta Decays.

We present the first lattice QCD calculation of the universal axial γW-box contribution □_{γW}^{VA} to both superallowed nuclear and neutron beta decays. This contribution emerges as a significant component within the theoretical uncertainties surrounding the extraction of |V_{ud}| from superallowed decays. Our calculation is conducted using two domain wall fermion ensembles at the physical pion mass. To construct the nucleon four-point correlation functions, we employ the random sparsening field technique. Furthermore, we incorporate long-distance contributions to the hadronic function using the infinite-volume reconstruction method. Upon performing the continuum extrapolation, we arrive at □_{γW}^{VA}=3.65(7)_{lat}(1)_{PT}×10^{-3}. Consequently, this yields a slightly higher value of |V_{ud}|=0.973 86(11)_{exp}(9)_{RC}(27)_{NS}, reducing the previous 2.1σ tension with the CKM unitarity to 1.8σ. Additionally, we calculate the vector γW-box contribution to the axial charge g_{A}, denoted as □_{γW}^{VV}, and explore its potential implications.

Dual N-Heterocyclic Carbene/Transition Metal Catalysis.

N-heterocyclic carbene catalysis has been developed as a versatile method for the enantioselective synthesis of complex organic molecules in organic chemistry. Merging of N-heterocyclic carbene catalysis with transition metal catalysis holds the potential to achieve unprecedented transformations with broad substrate scope and excellent stereoselectivity, which are unfeasible with individual catalyst. Thus, this dual catalysis has attracted increasing attention, and numerous elegant dual catalytic systems have been established. In this review, we summarize the recent achievements of dual NHC/transition metal catalysis, including the reaction design, mechanistic studies and practical applications.

Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

Autophagy in dry AMD: A promising therapeutic strategy for retinal pigment epithelial cell damage.

Dry age-related macular degeneration (AMD) is a prevalent clinical condition that leads to permanent damage to central vision and poses a significant threat to patients' visual health. Although the pathogenesis of dry AMD remains unclear, there is consensus on the role of retinal pigment epithelium (RPE) damage. Oxidative stress and chronic inflammation are major contributors to RPE cell damage, and the NOD-like receptor thermoprotein structural domain-associated protein 3 (NLRP3) inflammasome mediates the inflammatory response leading to apoptosis in RPE cells. Furthermore, lipofuscin accumulation results in oxidative stress, NLRP3 activation, and the development of vitelliform lesions, a hallmark of dry AMD, all of which may contribute to RPE dysfunction. The process of autophagy, involving the encapsulation, recognition, and transport of accumulated proteins and dead cells to the lysosome for degradation, is recognized as a significant pathway for cellular self-protection and homeostasis maintenance. Recently, RPE cell autophagy has been discovered to be closely linked to the development of macular degeneration, positioning autophagy as a cutting-edge research area in the realm of dry AMD. In this review, we present an overview of how lipofuscin, oxidative stress, and the NLRP3 inflammasome damage the RPE through their respective causal mechanisms. We summarized the connection between autophagy, oxidative stress, and NLRP3 inflammatory cytokines. Our findings suggest that targeting autophagy improves RPE function and sustains visual health, offering new perspectives for understanding the pathogenesis and clinical management of dry AMD.