Commercial Nafion Membranes for Harvesting Osmotic Energy from Proton Gradients that Exceed the Commercial Goal of 5.0 W/m2.

Osmotic energy from proton gradients in industrial acidic wastewater can be harvested and converted to electricity through membranes, making it a renewable and sustainable power source. However, the currently designed membranes for harvesting proton gradient energy in acidic wastewater cannot simultaneously achieve excellent chemical/mechanical stability and high power density under a large-scale area and require high cost and complex operations. Here, we demonstrate that commercial Nafion membranes with high chemical/mechanical stability and proton transport selectivity can generate a power density of 5.1 W/m2 for harvesting osmotic energy from proton gradients under a test area of 0.2 mm2, which exceeds the commercial goal of 5.0 W/m2. Even under a test area of 12.5 mm2, a power density of 2.1 W/m2 can be achieved under a strong acid condition. In addition, the heat can greatly promote proton transport, and the power density is increased, i.e., 8.1 W/m2 at 333 K (5.1 W/m2 at 293 K) under a test area of 0.2 mm2. By matching membranes with ion selectivity, our work demonstrates the potential of Nafion membranes for harvesting proton gradient energy in acidic wastewater and provides an approach for large-scale conversion of osmotic energy.

Intestinal Barrier Dysfunction and Gut Microbiota in Non-Alcoholic Fatty Liver Disease: Assessment, Mechanisms, and Therapeutic Considerations.

Non-alcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury closely related to insulin resistance (IR) and genetic susceptibility without alcohol consumption, which encompasses a spectrum of liver disorders ranging from simple hepatic lipid accumulation, known as steatosis, to the more severe form of steatohepatitis (NASH). NASH can progress to cirrhosis and hepatocellular carcinoma (HCC), posing significant health risks. As a multisystem disease, NAFLD is closely associated with systemic insulin resistance, central obesity, and metabolic disorders, which contribute to its pathogenesis and the development of extrahepatic complications, such as cardiovascular disease (CVD), type 2 diabetes mellitus, chronic kidney disease, and certain extrahepatic cancers. Recent evidence highlights the indispensable roles of intestinal barrier dysfunction and gut microbiota in the onset and progression of NAFLD/NASH. This review provides a comprehensive insight into the role of intestinal barrier dysfunction and gut microbiota in NAFLD, including intestinal barrier function and assessment, inflammatory factors, TLR4 signaling, and the gut-liver axis. Finally, we conclude with a discussion on the potential therapeutic strategies targeting gut permeability and gut microbiota in individuals with NAFLD/NASH, such as interventions with medications/probiotics, fecal transplantation (FMT), and modifications in lifestyle, including exercise and diet.

Scalable Fabrication of Ionic-Conductive Covalent Organic Framework Fibers for Capturing of Sustainable Osmotic Energy.

High-performance covalent organic framework (COF) fibers are demanded for an efficient capturing of blue osmotic power because of their excellent durability, simple integration, and large scalability. However, the scalable production of COF fibers is still very challenging due to the poor solubility and fragile structure of COFs. Herein, for the first time, it is reported that COF dispersions can be continuously processed into macroscopic, meter-long, and pure COF fibers using a wet spinning approach. The two presented COF fibers can be directly used for capturing of osmotic energy, avoiding the production of composite materials that require other additives and face challenges such as phase separation and environmental issues induced by the additives. A COF fiber exhibits power densities of 70.2 and 185.3 W m-2 at 50-fold and 500-fold salt gradients, respectively. These values outperform those of most reported systems, which indicate the high potential of COF fibers for capturing of blue osmotic energy.

Long COVID and its association with neurodegenerative diseases: pathogenesis, neuroimaging, and treatment.

Corona Virus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has presented unprecedented challenges to the world. Changes after acute COVID-19 have had a significant impact on patients with neurodegenerative diseases. This study aims to explore the mechanism of neurodegenerative diseases by examining the main pathways of central nervous system infection of SARS-CoV-2. Research has indicated that chronic inflammation and abnormal immune response are the primary factors leading to neuronal damage and long-term consequences of COVID-19. In some COVID-19 patients, the concurrent inflammatory response leads to increased release of pro-inflammatory cytokines, which may significantly impact the prognosis. Molecular imaging can accurately assess the severity of neurodegenerative diseases in patients with COVID-19 after the acute phase. Furthermore, the use of FDG-PET is advocated to quantify the relationship between neuroinflammation and psychiatric and cognitive symptoms in patients who have recovered from COVID-19. Future development should focus on aggressive post-infection control of inflammation and the development of targeted therapies that target ACE2 receptors, ERK1/2, and Ca2+.

Source-free active domain adaptation for diabetic retinopathy grading based on ultra-wide-field fundus images.

Domain adaptation (DA) is commonly employed in diabetic retinopathy (DR) grading using unannotated fundus images, allowing knowledge transfer from labeled color fundus images. Existing DAs often struggle with domain disparities, hindering DR grading performance compared to clinical diagnosis. A source-free active domain adaptation method (SFADA), which generates features of color fundus images by noise, selects valuable ultra-wide-field (UWF) fundus images through local representation matching, and adapts models using DR lesion prototypes, is proposed to upgrade DR diagnostic accuracy. Importantly, SFADA enhances data security and patient privacy by excluding source domain data. It reduces image resolution and boosts model training speed by modeling DR grade relationships directly. Experiments show SFADA significantly improves DR grading performance, increasing accuracy by 20.90% and quadratic weighted kappa by 18.63% over baseline, reaching 85.36% and 92.38%, respectively. This suggests SFADA's promise for real clinical applications.

Automatic ultrasensitive lateral flow immunoassay based on a color-enhanced signal amplification strategy.

Lateral flow immunoassays (LFIAs) are an essential and widely used point-of-care test for medical diagnoses. However, commercial LFIAs still have low sensitivity and specificity. Therefore, we developed an automatic ultrasensitive dual-color enhanced LFIA (DCE-LFIA) by applying an enzyme-induced tyramide signal amplification method to a double-antibody sandwich LFIA for antigen detection. The DCE-LFIA first specifically captured horseradish peroxidase (HRP)-labeled colored microspheres at the Test line, and then deposited a large amount of tyramide-modified signals under the catalytic action of HRP to achieve the color superposition. A limit of detection (LOD) of 3.9 pg/mL and a naked-eye cut-off limit of 7.8 pg/mL were achieved for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein. Additionally, in the inactivated virus detections, LOD equivalent to chemiluminescence (0.018 TCID50/mL) was obtained, and it had excellent specificity under the interference of other respiratory viruses. High sensitivity has also been achieved for detection of influenza A, influenza B, cardiac troponin I, and human chorionic gonadotrophin using this DCE-LFIA, suggesting the assay is universally applicable. To ensure the convenience and stability in practical applications, we created an automatic device. It provides a new practical option for point-of-care test immunoassays, especially ultra trace detection and at-home testing.

Dual-Activated H2O2-Responsive AIE Probes for Oocyte Quality Assessment.

Nonobstructive azoospermia (NOA) is an important cause of infertility, and intracytoplasmic sperm injection (ICSI) is the mainstay of treatment for these patients. In cases where a sufficient number of sperm (usually 1-2) is not available, the selection of oocytes for ICSI is a difficult problem that must be solved. Here, we constructed a dual-activated oxidative stress-responsive AIE probe, b-PyTPA. The strong donor-acceptor configuration of b-PyTPA leads to twisted intramolecular charge transfer (TICT) effect that quenches the fluorescence of the probe, however, H2O2 would specifically remove the boronatebenzyl unit and release a much weaker acceptor, which inhibits TICT and restores the fluorescence. In addition, the presence of a pyridine salt makes b-PyTPA more hydrophilic, whereas removal of the pyridine salt increases the hydrophobicity of PyTPA, which triggers aggregation and further enhances fluorescence. Thus, the higher the intracellular level of oxidative stress, the stronger the fluorescence. In vitro, this dual-activated fluorescent probe is capable of accurately detecting senescent cells (high oxidative stress). More importantly, b-PyTPA was able to characterize senescent oocytes, as assessed by the level of oxidative stress. It is also possible to identify high quality oocytes from those obtained for subsequent ICSI. In conclusion, this dual-activated oxidative stress-assessment probe enables the quality assessment of oocytes and has potential application in ICSI.

A Self-Powered Biochemical Sensor for Intelligent Agriculture Enabled by Signal Enhanced Triboelectric Nanogenerator.

Precise agriculture based on intelligent agriculture plays a significant role in sustainable development. The agricultural Internet of Things (IoTs) is a crucial foundation for intelligent agriculture. However, the development of agricultural IoTs has led to exponential growth in various sensors, posing a major challenge in achieving long-term stable power supply for these distributed sensors. Introducing a self-powered active biochemical sensor can help, but current sensors have poor sensitivity and specificity making this application challenging. To overcome this limitation, a triboelectric nanogenerator (TENG)-based self-powered active urea sensor which demonstrates high sensitivity and specificity is developed. This device achieves signal enhancement by introducing a volume effect to enhance the utilization of charges through a novel dual-electrode structure, and improves the specificity of urea detection by utilizing an enzyme-catalyzed reaction. The device is successfully used to monitor the variation of urea concentration during crop growth with concentrations as low as 4 µm, without being significantly affected by common fertilizers such as potassium chloride or ammonium dihydrogen phosphate. This is the first self-powered active biochemical sensor capable of highly specific and highly sensitive fertilizer detection, pointing toward a new direction for developing self-powered active biochemical sensor systems within sustainable development-oriented agricultural IoTs.

Addressing Challenges in Ion-Selectivity Characterization in Nanopores.

Ion selectivity is the basis for designing smart nanopore/channel-based devices, e.g., ion separators and biosensors. Quantitative characterization of ion selectivities in nanopores often employs the Nernst or Goldman-Hodgkin-Katz (GHK) equation to interpret transmembrane potentials. However, the direction of the measured transmembrane potential drop is not specified in these equations, and selectivity values calculated using absolute values of transmembrane potentials do not directly reveal the ion for which the membrane is selective. Moreover, researchers arbitrarily choose whether to use the Nernst or GHK equation and overlook the significant differences between them, leading to ineffective quantitative comparisons between studies. This work addresses these challenges through (a) specifying the transmembrane potential (sign) and salt concentrations in terms of working and reference electrodes and the solutions in which they reside when using the Nernst and GHK equations, (b) reporting of both Nernst-selectivity and GHK-selectivity along with solution compositions and transmembrane potentials when comparing different nanopores/channels, and (c) performing simulations to define an ideal selectivity for nanochannels. Experimental and modeling studies provide significant insight into these fundamental equations and guidelines for the development of nanopore/channel-based devices.

Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma.

Glaucoma is characterized by the progressive degeneration of retinal ganglion cells (RGCs) and their axons, and its risk increases with aging. Yet comprehensive insights into the complex mechanisms are largely unknown. Here, we found that anti-aging molecule Sirt6 was highly expressed in RGCs. Deleting Sirt6 globally or specifically in RGCs led to progressive RGC loss and optic nerve degeneration during aging, despite normal intraocular pressure (IOP), resembling a phenotype of normal-tension glaucoma. These detrimental effects were potentially mediated by accelerated RGC senescence through Caveolin-1 upregulation and by the induction of mitochondrial dysfunction. In mouse models of high-tension glaucoma, Sirt6 level was decreased after IOP elevation. Genetic overexpression of Sirt6 globally or specifically in RGCs significantly attenuated high tension-induced degeneration of RGCs and their axons, whereas partial or RGC-specific Sirt6 deletion accelerated RGC loss. Importantly, therapeutically targeting Sirt6 with pharmacological activator or AAV2-mediated gene delivery ameliorated high IOP-induced RGC degeneration. Together, our studies reveal a critical role of Sirt6 in preventing RGC and optic nerve degeneration during aging and glaucoma, setting the stage for further exploration of Sirt6 activation as a potential therapy for glaucoma.

Pore-Size-Dependent Role of Functional Elements at the Outer Surface and Inner Wall in Single-Nanochannel Biosensors.

Biological nanopores feature functional elements on the outer surfaces (FEOS) and inner walls (FEIW), enabling precise control over ions and molecules with exceptional sensitivity and specificity. This provides valuable inspiration to scientists for the development of intelligent artificial nanochannel-based platforms, with a wide range of potential applications, including biosensors. Much effort has been dedicated to investigating the distinct contribution of FEOS and FEIW of multichannel membrane biosensors. However, the intricate interactions among neighboring pores in multichannel biosensors have presented challenges. This underscores the untapped potential of single nanochannels as ideal candidates in this field. Here, we employed single nanochannel membranes with different pore sizes to investigate the distinct contributions of FEIW and FEOS to single-nanochannel biosensors, combined with numerical simulations. Our findings revealed that alterations in the negative charges of FEIW and FEOS, induced by target binding, have differential effects on ion transport, contingent upon the degree of nanoconfinement. In the case of smaller pores, such as 20 nm, the ion concentration polarization driven by FEIW can independently control ion transport through the surface's electric double layer. However, as the pore size increases to 40-60 nm, both FEIW and FEOS become essential for effective ion concentration polarization. When the pore size reaches 100 nm, both FEIW and FEOS are ineffective and thus unsuitable for biosensors. Simulations demonstrate that the observed phenomena can be attributed to the interactions between the charges of FEIW and FEOS within the overlapping electric double layer under confinement. These results underscore the critical role of pore size as a key parameter in governing the functionality of probes within or on nanopore-based biosensors as well as in the design of nanopore-based devices.

Metal nanoparticles for cancer therapy: Precision targeting of DNA damage.

Cancer, a complex and heterogeneous disease, arises from genomic instability. Currently, DNA damage-based cancer treatments, including radiotherapy and chemotherapy, are employed in clinical practice. However, the efficacy and safety of these therapies are constrained by various factors, limiting their ability to meet current clinical demands. Metal nanoparticles present promising avenues for enhancing each critical aspect of DNA damage-based cancer therapy. Their customizable physicochemical properties enable the development of targeted and personalized treatment platforms. In this review, we delve into the design principles and optimization strategies of metal nanoparticles. We shed light on the limitations of DNA damage-based therapy while highlighting the diverse strategies made possible by metal nanoparticles. These encompass targeted drug delivery, inhibition of DNA repair mechanisms, induction of cell death, and the cascading immune response. Moreover, we explore the pivotal role of physicochemical factors such as nanoparticle size, stimuli-responsiveness, and surface modification in shaping metal nanoparticle platforms. Finally, we present insights into the challenges and future directions of metal nanoparticles in advancing DNA damage-based cancer therapy, paving the way for novel treatment paradigms.

Low-dose radiotherapy synergizes with iRGD-antiCD3-modified T cells by facilitating T cell infiltration.

BACKGROUND AND PURPOSE: Poor penetration of transferred T cells represents a critical factor impeding the development of adoptive cell therapy in solid tumors. We demonstrated that iRGD-antiCD3 modification promoted both T cell infiltration and activation in our previous work. Interest in low-dose radiotherapy has recently been renewed due to its immuno-stimulatory effects including T cell recruitment. This study aims to explore the synergistic effects between low-dose radiotherapy and iRGD-antiCD3-modified T cells. MATERIALS AND METHODS: Flow cytometry was performed to assess the expression of iRGD receptors and chemokines. T cell infiltration was evaluated by immunohistofluorescence and in vivo real-time fluorescence imaging and antitumor effects were investigated by in vivo bioluminescence imaging in the gastric cancer peritoneal metastasis mouse model. RESULTS: We found that 2 Gy irradiation upregulated the expression of all three iRGD receptors and T-cell chemokines. The addition of 2 Gy low-dose irradiation boosted the accumulation and penetration of iRGD-antiCD3-modified T cells in peritoneal tumor nodules. Combining 2 Gy low-dose irradiation with iRGD-antiCD3-modified T cells significantly inhibited tumor growth and prolonged survival in the peritoneal metastasis mouse model with a favorable safety profile. CONCLUSION: Altogether, we demonstrated that low-dose radiotherapy could improve the antitumor potency of iRGD-antiCD3-modified T cells by promoting T cell infiltration, providing a rationale for exploring low-dose radiotherapy in combination of other adoptive T cell therapies in solid tumors.

Outer-Surface Functionalized Solid-State Nanochannels for Enhanced Sensing Properties: Progress and Perspective.

Solid-state nanochannel-based sensing systems have been established as vigorous tools for sensing plentiful biomarkers due to their label-free, highly sensitive, and high-throughput screening. However, research on solid-state nanochannels has predominantly centered on the functional groups modified on the inner wall, neglecting investigations into the outer surface. Actually, the outer surface, as a part of the nanochannels, also plays a key role in regulating ionic current. When the target nears the entrance of the nanochannel and prepares to pass through, it would also interact with functional groups located on the nanochannel's outer surface, leading to subsequent alterations in the ionic current. Recently, the probes on the outer surface have experimentally demonstrated their ability to independently regulate ionic current, unveiling advantages in in situ target detection, especially for targets larger than the diameter of the nanochannels that cannot pass through them. Here, we review the progress over the past decade in nanochannels featuring diverse outer-surface functionalization aimed at enhanced sensing performance, including charge modification, wettability adjustment, and probe immobilization. In addition, we present the promises and challenges posed by outer-surface functionalized nanochannels and discuss possible directions for their future deployments.

A Universal and Programmable Platform based on Fluorescent Peptide-Conjugated Probes for Detection of Proteins in Organelles of Living Cells.

Realizing protein analysis in organelles of living cells is of great significance for developing diagnostic and therapeutic methods of diseases. Fluorescent-labeled antibodies with well imaging performance and high affinity are classical biochemical tools for protein analysis, while due to the inability to effectively enter into cells, not to mention organelles and the uncontrollable reaction sites that might cause antibodies inactivation when chemically modification, they are hard to apply to living cells. Inspired by the structure of fluorescent-labeled antibodies, we designed as a universal detection platform that was based on the peptide-conjugated probes (PCPs) and consisted of three parts: a) a rotor type fluorescent molecular scaffold for conjugation and signal output; b) the cell penetration protein recognition unit; c) the subcellular organelle targeting unit. In living cells, PCPs could firstly localize at organelles and then proceed protein specific recognition, thus jointly leading to the restriction of twisted intramolecular charge transfer and activation of fluorescence signal. As a proof-of-concept, six different proteins in three typical intracellular organelles could be detected by our platform through simply replacing the recognition sequence of proteins and matching organelle targeting units. The position and intensity of fluorescence signals demonstrated specificity of PCPs and universality of the platform.

Association of aerobic and muscle-strengthening physical activity with all-cause and cardiovascular disease mortality among adults with type 2 diabetes: A prospective cohort of US adults.

OBJECTIVE: To investigate the relationship of moderate physical activity (MPA), vigorous physical activity (VPA), and muscle strengthening activity (MSA), independently and jointly, with all-cause, cardiovascular disease (CVD), and non-CVD mortality in individuals with type 2 diabetes (T2D). MATERIAL AND METHODS: This cohort study included 47,538 adults with T2D and 561,963 adults without T2D from the National Health Interview Survey 1997-2018 who provided data on self-reported physical activity (PA). Mortality data were obtained from the National Death Index through 2019. Cox regression was used to estimate hazard ratio (HR) and 95% confidence interval (CI). RESULTS: In analyses mutually adjusted, versus no MPA adults with T2D, performing the recommendations of MPA (150-299 min/week) associated with lower all-cause mortality (HR, 0.72; 95% CI, 0.66-0.78), CVD mortality (HR, 0.68; 95% CI, 0.58-0.79), and non-CVD mortality (HR, 0.72; 95% CI, 0.65-0.79). Similar benefits were observed in those meeting recommendations for VPA and MSA. Higher levels of PA beyond current recommendations may provide a few additional benefits without adverse effects on mortality risk, regardless of diabetes onset age, duration of diabetes, and medication status. The joint analysis indicates that combining MSA with aerobic PA could further lower mortality risk, and lowest all-cause mortality was observed among individuals engaging in either 75-150 min/week of VPA and 1 time/week of MSA (HR, 0.30; 95% CI, 0.13-0.70) or 150-299 min/week of MPA and 1 time/week of MSA (HR, 0.33; 95% CI, 0.20-0.55). CONCLUSION: Our study supports the current PA guidelines and suggests that there may be limited benefits gained from exercising beyond recommended levels in adults with T2D, combining recommended levels of aerobic and resistance exercises could yield the greatest benefits.

The NLRP3 inhibitor, OLT1177 attenuates brain injury in experimental intracerebral hemorrhage.

BACKGROUND AND PURPOSE: It has been reported activation of NLRP3 inflammasome after intracerebral hemorrhage (ICH) ictus exacerbates neuroinflammation and brain injury. We hypothesized that inhibition of NLRP3 by OLT1177 (dapansutrile), a novel NLRP3 inflammasome inhibitor, could reduce brain edema and attenuate brain injury in experimental ICH. METHODS: ICH was induced by injection of autologous blood into basal ganglia in mice models. Sixty-three C57Bl/6 male mice were randomly grouped into the sham, vehicle, OLT1177 (Dapansutrile, 200 mg/kg intraperitoneally) and treated for consecutive three days, starting from 1 h after ICH surgery. Behavioral test, brain edema, brain water content, blood-brain barrier integrity and vascular permeability, cell apoptosis, and NLRP3 and its downstream protein levels were measured. RESULTS: OLT1177 significantly reduced cerebral edema after ICH and contributed to the attenuation of neurological deficits. OLT1177 could preserve blood-brain barrier integrity and lessen vascular leakage. In addition, OLT1177 preserved microglia morphological shift and significantly inhibited the activation of caspase-1 and release of IL-1ß. We also found that OLT1177 can protect against neuronal loss in the affected hemisphere. CONCLUSIONS: OLT1177 (dapansutrile) could significantly attenuate the brain edema after ICH and effectively alleviate the neurological deficit. This result suggests that the novel NLRP3 inhibitor, OLT1177, might serve as a promising candidate for the treatment of ICH.

Emerging Data Processing Methods for Single-Entity Electrochemistry.

Single-entity electrochemistry is a powerful tool that enables the study of electrochemical processes at interfaces and provides insights into the intrinsic chemical and structural heterogeneities of individual entities. Signal processing is a critical aspect of single-entity electrochemical measurements and can be used for data recognition, classification, and interpretation. In this review, we summarize the recent five-year advances in signal processing techniques for single-entity electrochemistry and highlight their importance in obtaining high-quality data and extracting effective features from electrochemical signals, which are generally applicable in single-entity electrochemistry. Moreover, we shed light on electrochemical noise analysis to obtain single-molecule frequency fingerprint spectra that can provide rich information about the ion networks at the interface. By incorporating advanced data analysis tools and artificial intelligence algorithms, single-entity electrochemical measurements would revolutionize the field of single-entity analysis, leading to new fundamental discoveries.

Magneto-Induced Janus Adhesive-Tough Hydrogels for Wearable Human Motion Sensing and Enhanced Low-Grade Heat Harvesting.

Janus hydrogels with different properties on the two surfaces have considerable potential in the field of material engineering applications. Various Janus hydrogels have been developed, but there are still some problems, such as stress mismatch caused by the double-layer structure and Janus failure caused by material diffusion in the gradient structure. Here, we report a Janus adhesive-tough hydrogel with polydopamine-decorated Fe3O4 nanoparticles (Fe3O4@PDA) at one side induced by magnetic field to avoid uncontrollable material diffusion in the cross-linking polymerization of acrylamide with alginate-calcium. The magneto-induced Janus (MIJ) hydrogel has an adhesive surface and a tough bulk without an obvious interface to avoid stress mismatch. Due to the intrinsic dissipative matrix and the abundant catechol groups on the adhesive surface, it shows strong adhesion onto various substrates. The MIJ hydrogel has high sensitivity (GF = 0.842) in detecting tiny human motion. Owing to the synergy of Fe3O4@PDA-enhanced interfacial adhesion and heat transfer, it is possible to quickly generate effective temperature differences when adhering to human skin. The MIJ hydrogel achieves a Seebeck coefficient of 13.01 mV·K-1 and an output power of 462.02 mW·m-2 at a 20 K temperature difference. This work proposes a novel strategy to construct Janus hydrogels for flexible wearable devices in human motion sensing and low-grade heat harvesting.

Serum metabolome and gut microbiome alterations are associated with low handgrip strength in older adults.

Handgrip strength (HGS), which represents global muscle strength, is a powerful indicator of disability and mortality in older adults; it is also used for the diagnosis of possible- or probable- sarcopenia and physical frailty. This study aimed to explore the metabolic mechanisms and potential biomarkers associated with declining HGS among older adults. We recruited 15 age- and environment-matched inpatients (age, 77-90 years) with low or normal HGS. Liquid chromatography-mass spectrometry (LC-MS) and 16S ribosomal DNA (rDNA) gene sequencing were performed to analyze the metabolome of serum and stool samples and the gut microbiome composition of stool samples. Spearman's correlation analysis was used to identify the potential serum and fecal metabolites associated with HGS. We assessed the levels of serum and fecal metabolites belonging to the class of cinnamic acids and derivatives and reported that the levels of carboxylic acids and their derivatives decreased in the low-HGS group. Serum levels of microbial metabolites, including cinnamoylglycine, 4-methoxycinnamic acid, and (e)-3,4,5-trimethoxycinnamic acid, were positively correlated with HGS. We found that gut microbial α-diversity was significantly higher in the low-HGS group, whereas higher ß-diversity was observed in the normal group. The relative abundances of the genera Parabacteroides and Intestinibacter increased significantly in the low-HGS group and were negatively correlated with the serum levels of cinnamoylglycine. The identified metabolites whose levels were markedly altered, and intestinal flora associated with these metabolites suggest the potential metabolic underpinnings for HGS and provide a basis for the further identification of biomarkers of muscle strength decline in older adults.