In Situ Triggered Self-Contraction Bioactive Microgel Assembly Accelerates Diabetic Skin Wound Healing by Activating Mechanotransduction and Biochemical Pathway.

Chronic nonhealing skin wounds, characterized by reduced tissue contractility and inhibited wound cell survival under hyperglycemia and hypoxia, present a significant challenge in diabetic care. Here, an advanced self-contraction bioactive core-shell microgel assembly with robust tissue-adhesion (SMART-EXO) is introduced to expedite diabetic wound healing. The SMART-EXO dressing exhibits strong, reversible adhesion to damaged tissue due to abundant hydrogen and dynamic coordination bonds. Additionally, the core-shell microgel components and dynamic coordination bonds provide moderate rigidity, customizable self-contraction, and an interlinked porous architecture. The triggered in situ self-contraction of the SMART-EXO dressing enables active, tunable wound contraction, activating mechanotransduction in the skin and promoting the optimal fibroblast-to-myofibroblast conversion, collagen synthesis, and angiogenesis. Concurrently, the triggered contraction of SMART-EXO facilitates efficient loading and on-demand release of bioactive exosomes, contributing to re-epithelialization and wound microenvironment regulation in diabetic mice. RNA-seq results reveal the activation of critical signaling pathways associated with mechanosensing and exosome regulation, highlighting the combined biomechanical and biochemical mechanisms. These findings underscore SMART-EXO as a versatile, adaptable solution to the complex challenges of diabetic wound care.

Bioactive nanocomposite hydrogel enhances postoperative immunotherapy and bone reconstruction for osteosarcoma treatment.

Osteosarcoma, a malignant bone tumor often characterized by high hedgehog signaling activity, residual tumor cells, and substantial bone defects, poses significant challenges to both treatment response and postsurgical recovery. Here, we developed a nanocomposite hydrogel for the sustained co-delivery of bioactive magnesium ions, anti-PD-L1 antibody (αPD-L1), and hedgehog pathway antagonist vismodegib, to eradicate residual tumor cells while promoting bone regeneration post-surgery. In a mouse model of tibia osteosarcoma, this hydrogel-mediated combination therapy led to remarkable tumor growth inhibition and hence increased animal survival by enhancing the activity of tumor-suppressed CD8+ T cells. Meanwhile, the implanted hydrogel improved the microenvironment of osteogenesis through long-term sustained release of Mg2+, facilitating bone defect repair by upregulating the expression of osteogenic genes. After 21 days, the expression levels of ALP, COL1, RUNX2, and BGLAP in the Vis-αPD-L1-Gel group were approximately 4.1, 5.1, 5.5, and 3.4 times higher than those of the control, respectively. We believe that this hydrogel-based combination therapy offers a potentially valuable strategy for treating osteosarcoma and addressing the tumor-related complex bone diseases.

Orientation-Dependent Mechanical Behaviors of BCC-Fe in Light of the Thermo-Kinetic Synergy of Plastic Deformation.

The orientation-dependent mechanical behaviors of metallic alloys are governed by deformation mechanisms, but the underlying physics remain to be explored. In this work, the mechanical responses along different orientations and behind the mechanisms of BCC-Fe are investigated by performing molecular dynamic simulations. It is found that the mechanical properties of BCC-Fe exhibit apparent anisotropic characteristics. The <100>-oriented BCC-Fe presents a Young's modulus of E = 147.56 GPa, a strength of σy = 10.15 GPa, and a plastic strain of εy = 0.084 at the yield point, whereas the <111> orientation presents E = 244.84 GPa, σy = 27.57 GPa, and εy = 0.21. Based on classical dislocation theory, the reasons for such orientation-dependent mechanical behaviors are analyzed from the perspective of thermo-kinetic synergy upon deformation. It turns out that the anisotropic mechanical responses of BCC-Fe are associated with the magnitude of the thermodynamic driving force (ΔG) and kinetic energy barrier (Q) for dislocation motion, which dominate the corresponding deformation mechanism. Compared with the low ΔG (6.395 GPa) and high Q (11.95 KJ/mol) of the <100>-oriented BCC-Fe dominated by deformation twinning, the <111> orientation governed by dislocation slip presents a high ΔG (17.37 GPa) and low Q (6.45 KJ/mol). Accordingly, the orientation-dependent deformation behaviors of BCC-Fe are derived from the thermo-kinetic synergy for dislocation motion.

Internet Use and Loneliness Among Urban and Non-Urban Chinese Older Adults: The Roles of Family Support, Friend Support, and Social Participation.

OBJECTIVES: This study investigated the association between internet use and loneliness among older Chinese adults, and the mediating effects of family support, friend support, and social participation. These associations were evaluated in the context of urban and non-urban geographic settings. METHODS: This study used data from the 2018 wave of the China Longitudinal Ageing Social Survey (N = 10,126), examining samples of urban (n = 3,917) and non-urban (n = 6,209) older adults separately. Linear regression and path analysis within a structural equation modeling framework were employed. RESULTS: Internet use was negatively associated with loneliness for both urban and non-urban residing older adults. Family support and social participation mediated the association between internet use and loneliness for both urban and non-urban residing older Chinese adults, but friend support mediated this association only for urban older residents. DISCUSSION: This study shed light on our understanding of the relationship between internet use and loneliness among older adults in the Chinese context. Also, these findings suggested that digital interventions for loneliness should pay special attention to the different characteristics of urban and non-urban dwelling older Chinese adults.

Host-Guest Interaction Mediated Interfacial Co-Assembly of Cyclodextrin and Bottlebrush Surfactants for Precisely Tunable Photonic Supraballs.

Investigations of host-guest interactions at water-oil (w/o) interfaces are limited in single emulsion systems producing simple self-assembled objects with limited uses. Here, within hierarchically ordered water-in-oil-in-water (w/o/w) multiple emulsion droplets, interfacial self-assembly of (polynorbornene-graft-polystyrene)-block-(polynorbornene-graft-polyethylene glycol) (PNPS-b-PNPEG) bottlebrush block copolymers can be precisely controlled through host-guest interactions. α-Cyclodextrin (α-CD) in the aqueous phase can thread onto PEG side chains of the bottlebrush surfactants adsorbed at the w/o interface, leading to dehydration and collapsed chain conformation of the PEG block. Consequently, spherical curvature of the w/o internal droplets increases with the increased asymmetry of the bottlebrush molecules, producing photonic supraballs with precisely tailored structural parameters as well as photonic bandgaps. This work provides a simple but highly effective strategy for precise manipulation of complex emulsion systems applicable in a variety of applications, such as photonic pigments, cosmetic products, pesticides, artificial cells, etc.

Photonic control of ligand nanospacing in self-assembly regulates stem cell fate.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of "closely nanospaced" ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with "closely nanospaced" ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of "distantly nanospaced" ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Surface hydrophobization of hydrogels via interface dynamics-induced network reconfiguration.

Effective and easy regulation of hydrogel surface properties without changing the overall chemical composition is important for their diverse applications but remains challenging to achieve. We report a generalizable strategy to reconfigure hydrogel surface networks based on hydrogel-substrate interface dynamics for manipulation of hydrogel surface wettability and bioadhesion. We show that the grafting of hydrophobic yet flexible polymeric chains on mold substrates can significantly elevate the content of hydrophobic polymer backbones and reduce the presence of polar groups in hydrogel surface networks, thereby transforming the otherwise hydrophilic hydrogel surface into a hydrophobic surface. Experimental results show that the grafted highly dynamic hydrophobic chains achieved with optimal grafting density, chain length, and chain structure are critical for such substantial hydrogel surface network reconfiguration. Molecular dynamics simulations further reveal the atomistic details of the hydrogel network reconfiguration induced by the dynamic interface interactions. The hydrogels prepared using our strategy show substantially enhanced bioadhesion and transdermal delivery compared with the hydrogels of the same chemical composition but fabricated via the conventional method. Our findings provide important insights into the dynamic hydrogel-substrate interactions and are instrumental to the preparation of hydrogels with custom surface properties.

Positive Association of Urinary Dimethylarsinic Acid (DMAV) with Serum 25(OH)D in Adults Living in an Area of Water-Borne Arsenicosis in Shanxi, China.

Limited studies have demonstrated that inorganic arsenic exposure is positively associated with serum vitamin D levels, although the correlation between urinary arsenic species and serum vitamin D has not been investigated in areas of water-borne arsenicosis. A cross-sectional study of 762 participants was conducted in Wenshui Country, Shanxi Province, a water-borne arsenicosis area. The results showed a positive relationship between urinary arsenic species (inorganic arsenic (iAs), methylarsonic acid (MMAV), dimethylarsinic acid (DMAV) and serum 25(OH)D. Log-binomial regression analysis indicated a 0.4% increase in the risk of vitamin D excess for every 1-unit increment in the Box-Cox transformed urinary DMAV after adjustment for covariates. After stratifying populations by inorganic arsenic methylation metabolic capacity, serum 25(OH)D levels in the populations with iAs% above the median and primary methylation index (PMI) below the median increased by 0.064 ng/mL (95% CI: 0.032 to 0.096) for every one-unit increase in the Box-Cox transformed total arsenic (tAs) levels. Serum 25(OH)D levels increased by 0.592 ng/mL (95% CI: 0.041 to 1.143) for every one-unit rise in the Box-Cox transformed iAs levels in people with skin hyperkeratosis. Overall, our findings support a positive relationship between urinary arsenic species and serum 25(OH)D. It was recommended that those residing in regions with water-borne arsenicosis should take moderate vitamin D supplements to avoid vitamin D poisoning.

Pathways Linking Information and Communication Technology Use and Loneliness Among Older Adults: Evidence From the Health and Retirement Study.

BACKGROUND AND OBJECTIVES: This study investigated the association between information and communication technology (ICT) use and loneliness among community-dwelling older adults (aged 65+), as well as the mediating effects of social relations, perceived control, and purpose-in-life. RESEARCH DESIGN AND METHODS: The study used data from the 2014 and 2018 Health and Retirement Study (N = 3,026), employing autoregressive path models with contemporaneous mediation to assess the association of 2 kinds of ICT use, social media communication and general computer use, with loneliness through the pathways of perceived social support, social contact, perceived constraints, and purpose-in-life. RESULTS: Social media communication had a negative association with loneliness. Perceived social support and social contact mediated this association, but not perceived constraints, or purpose-in-life. General computer use did not have a significant total effect on loneliness; however, a significant indirect effect through perceived constraints, purpose-in-life, and social contact was found. DISCUSSION AND IMPLICATIONS: Our findings extended the existing literature regarding the important factors associated with variation in loneliness among older adults. Health programs and ICT solutions could be more effective in mitigating loneliness if they target the root causes of loneliness, including reducing perceptions of constraints and increasing a sense of purpose-in-life, along with strengthening social relationships.

Internet use and loneliness among older Chinese adults.

OBJECTIVES: This study examined the association between Internet use and loneliness among Chinese older adults (aged 60+) over a two-year period using nationally representative survey data from China. METHODS: Using data from the 2016 and 2018 waves of the China Longitudinal Ageing Social Survey (N = 8,059), we estimated difference-in-differences regression models to assess the association between Internet use and levels of loneliness over time. RESULTS: Compared to Internet non-users, Chinese older adults who were new Internet users, as well as those who were continuous Internet users, reported lower levels of loneliness over time (B = -0.21, p < 0.001 and B = -0.16, p < 0.001, respectively). Conversely, those Chinese older adults who used the Internet in wave 1 but then disengaged from using the Internet in wave 2 demonstrated an upward trend in loneliness over time, similar to Internet non-users (the estimate of difference-in-differences was non-significant for the comparison between disengaged-users and non-users: B = -0.03, p = 0.42). CONCLUSION: This study provided new evidence to support the potential benefits of Internet use for reducing the risk of loneliness among Chinese older adults. The findings suggested that supporting current Internet users to remain digitally engaged is as important as encouraging Internet non-users to cross the digital divide.

Cu(II)@MXene based photothermal hydrogel with antioxidative and antibacterial properties for the infected wounds.

The regeneration of skin tissue is often impeded by bacterial infection seriously. At the same time, reactive oxygen species (ROS) are often overexpressed in infected skin wounds, causing persistent inflammation that further hinders the skin repair process. All of these make the treatment of infected wounds is still a great challenge in clinic. In this study, we fabricate Cu(II)@MXene photothermal complex based on electrostatic self-assembly between Cu2+ and MXene, which are then introduced into a hyaluronic acid (HA) hydrogel to form an antibacterial dressing. The rapid adhesion, self-healing, and injectability of the dressing allows the hydrogel to be easily applied to different wound shapes and to provide long-term wound protection. More importantly, this easily prepared Cu(II)@MXene complex can act as a photothermal antibacterial barrier, ROS scavenger and angiogenesis promoter simultaneously to accelerate the healing rate of infected wounds. Our in vivo experiments strongly proved that the inflammatory condition, collagen deposition, vessel formation, and the final wound closure area were all improved by the application of Cu(II)@MXene photothermal hydrogel dressing.

The disruption of blood-brain barrier induced by long-term arsenic exposure is associated with the increase of MMP-9 and MMP-2: The characteristics are similar to those caused by senescence.

Accumulating evidence suggests that Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) are involved in the neuropathological processes by contributing to breaking the extracellular matrix and the tight junctions that constitute the blood-brain barrier (BBB). However, the influences of arsenic (As) on these two MMPs were inconsistent. In the cross-sectional study of 500 adults, serum MMP-2 and MMP-9 positively correlated with urine arsenic. And the positive correlation between urine tAs and serum MMP-9/2 was found in people older than 59 years. In vivo studies, we found that arsenic exposure or senescence might decrease number of neurons and neuritic density and increase serum and cortical MMP-9/2 levels. Furthermore, arsenic exposure or senescence could disrupt the tight junction of BBB and elevate MMP-9 and MMP-2 expression in the cerebral microvascular endothelium. The MMP-9 and MMP-2 are of particular interest when researching the link between arsenic exposure and nerve damage.

AUV Path Planning Considering Ocean Current Disturbance Based on Cloud Desktop Technology.

In the field of ocean energy detection, Autonomous Underwater Vehicles (AUVs) offer significant advantages in terms of manpower, resource, and energy efficiency. However, the unpredictable nature of the ocean environment, particularly the real-time changes in ocean currents, poses navigational risks for AUVs. Therefore, effective path planning in dynamic environments is crucial for AUVs to perform specific tasks. This paper addresses the static path planning problem and proposes a model called the noise net double DQN network with prioritized experience replay (N-DDQNP). The N-DDQNP model combines a noise network and a prioritized experience replay mechanism to address the limited exploration and slow convergence speed issues of the DQN algorithm, which are caused by the greedy strategy and uniform sampling mechanism. The proposed approach involves constructing a double DQN network with a priority experience replay and an exploration mechanism using the noise network. Second, a compound reward function is formulated to take into account ocean current, distance, and safety factors, ensuring prompt feedback during the training process. Regarding the ocean current, the reward function is designed based on the angle between the current direction and the AUV's heading direction, considering its impact on the AUV's speed. As for the distance factor, the reward is determined by the Euclidean distance between the current position and the target point. Furthermore, the safety factor considers whether the AUV may collide with obstacles. By incorporating these three factors, the compound reward function is established. To evaluate the performance of the N-DDQNP model, experiments were conducted using real ocean data in various complex ocean environments. The results demonstrate that the path planning time of the N-DDQNP model outperforms other algorithms in different ocean current scenarios and obstacle environments. Furthermore, a user console-AUV connection has been established using spice cloud desktop technology. The cloud desktop architecture enables intuitive observation of the AUV's navigation posture and the surrounding marine environment, facilitating safer and more efficient underwater exploration and marine resource detection tasks.

Complex coacervate-derived hydrogel with asymmetric and reversible wet bioadhesion for preventing UV light-induced morbidities.

Protecting the skin from UV light irradiation in wet and underwater environments is challenging due to the weak adhesion of existing sunscreen materials but highly desired. Herein we report a polyethyleneimine/thioctic acid/titanium dioxide (PEI/TA/TiO2) coacervate-derived hydrogel with robust, asymmetric, and reversible wet bioadhesion and effective UV-light-shielding ability. The PEI/TA/TiO2 complex coacervate can be easily obtained by mixing a PEI solution and TA/TiO2 powder. The fluid PEI/TA/TiO2 coacervate deposited on wet skin can spread into surface irregularities and subsequently transform into a hydrogel with increased cohesion, thereby establishing interdigitated contact and adhesion between the bottom surface and skin. Meanwhile, the functional groups between the skin and hydrogel can form physical interactions to further enhance bioadhesion, whereas the limited movement of amine and carboxyl groups on the top hydrogel surface leads to low adhesion. Therefore, the coacervate-derived hydrogel exhibits asymmetric adhesiveness on the bottom and top surfaces. Moreover, the PEI/TA/TiO2 hydrogel formed on the skin could be easily removed using a NaHCO3 aqueous solution without inflicting damage. More importantly, the PEI/TA/TiO2 hydrogel can function as an effective sunscreen to block UV light and prevent UV-induced MMP-9 overexpression, inflammation, and DNA damage in animal skin. The advantages of PEI/TA/TiO2 coacervate-derived hydrogels include robust, asymmetric, and reversible wet bioadhesion, effective UV light-shielding ability, excellent biocompatibility, and easy preparation and usage, making them a promising bioadhesive to protect the skin from UV light-associated damage in wet and underwater environments.

Mechanical manipulation of cancer cell tumorigenicity via heat shock protein signaling.

Biophysical cues of rigid tumor matrix play a critical role in cancer cell malignancy. We report that stiffly confined cancer cells exhibit robust growth of spheroids in the stiff hydrogel that exerts substantial confining stress on the cells. The stressed condition activated Hsp (heat shock protein)-signal transducer and activator of transcription 3 signaling via the transient receptor potential vanilloid 4-phosphatidylinositol 3-kinase/Akt axis, thereby up-regulating the expression of the stemness-related markers in cancer cells, whereas these signaling activities were suppressed in cancer cells cultured in softer hydrogels or stiff hydrogels with stress relief or Hsp70 knockdown/inhibition. This mechanopriming based on three-dimensional culture enhanced cancer cell tumorigenicity and metastasis in animal models upon transplantation, and pharmaceutically inhibiting Hsp70 improved the anticancer efficacy of chemotherapy. Mechanistically, our study reveals the crucial role of Hsp70 in regulating cancer cell malignancy under mechanically stressed conditions and its impacts on cancer prognosis-related molecular pathways for cancer treatments.

Online engagement, resilience, and loneliness among older people during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic exacerbated the public health concerns of social isolation and loneliness for older people who are vulnerable due to their health conditions and more restrictive social measures. However studies revealed that many older adults demonstrated high resilience and remained emotionally stable during the pandemic, particularly those who had a broad engagement with online technology that could compensate for their isolation. Yet, little empirical research has examined explicitly the association between online engagement and loneliness among older adults, and the role resilience played in this relationship during the pandemic. This study contributed to the literature by addressing these research gaps. RESEARCH DESIGN AND METHODS: This study investigated the relationships between online engagement (sum of involvement in 31 online activities), resilience (sum of positive experiences and personal growth during COVID-19) and loneliness (mean of 11-items from the revised version of the UCLA loneliness scale) among community-dwelling older people (aged 60+), using national survey data from the 2020 Health and Retirement Study (HRS) collected during the COVID-19 pandemic (N = 3,552). RESULTS AND CONCLUSION: Online engagement was negatively associated with levels of loneliness (ß = -0.080, 95% CI [-0.118, -0.047]), and this association was partially mediated by levels of resilience (ß = -0.023, 95% CI [-0.031, -0.016]. The findings suggested that a broad integration of online technology into daily-life may have helped older people combat loneliness during the pandemic, and resilience could be one important mechanism that linked this association.

Bioinspired Tumor-Targeting and Biomarker-Activatable Cell-Material Interfacing System Enhances Osteosarcoma Treatment via Biomineralization.

Osteosarcoma is an aggressive malignant tumor that primarily develops in children and adolescents. The conventional treatments for osteosarcoma often exert negative effects on normal cells, and chemotherapeutic drugs, such as platinum, can lead to multidrug resistance in tumor cells. Herein, this work reports a new bioinspired tumor-targeting and enzyme-activatable cell-material interface system based on DDDEEK-pY-phenylboronic acid (SAP-pY-PBA) conjugates. Using this tandem-activation system, this work selectively regulates the alkaline phosphatase (ALP) triggered anchoring and aggregation of SAP-pY-PBA conjugates on the cancer cell surface and the subsequent formation of the supramolecular hydrogel. This hydrogel layer can efficiently kill osteosarcoma cells by enriching calcium ions from tumor cells and forming a dense hydroxyapatite layer. Owing to the novel antitumor mechanism, this strategy neither hurts normal cells nor causes multidrug resistance in tumor cells, thereby showing an enhanced tumor treatment effect than the classical antitumor drug, doxorubicin (DOX). The outcome of this research demonstrates a new antitumor strategy based on a bioinspired enzyme-responsive biointerface combining supramolecular hydrogels with biomineralization.

Current Knowledge of Th22 Cell and IL-22 Functions in Infectious Diseases.

T helper 22 (Th22) cells, a newly defined CD4+ T-cell lineage, are characterized by their distinct cytokine profile, which primarily consists of IL-13, IL-22 and TNF-α. Th22 cells express a wide spectrum of chemokine receptors, such as CCR4, CCR6 and CCR10. The main effector molecule secreted by Th22 cells is IL-22, a member of the IL-10 family, which acts by binding to IL-22R and triggering a complex downstream signaling system. Th22 cells and IL-22 have been found to play variable roles in human immunity. In preventing the progression of infections such as HIV and influenza, Th22/IL-22 exhibited protective anti-inflammatory characteristics, and their deleterious proinflammatory activities have been demonstrated to exacerbate other illnesses, including hepatitis B and Helicobacter pylori infection. Herein, we review the current understanding of Th22 cells, including their definition, differentiation and mechanisms, and the effect of Th22/IL-22 on human infectious diseases. According to studies on Th22 cells, Th22/IL-22 may be a promising therapeutic target and an effective treatment strategy for various infections.

Kangyi Qiangshen Gong exercise prescription for pulmonary function and quality of life in patients recovered from COVID-19: a study protocol for a randomized controlled trial.

BACKGROUND: Since early 2022, patients with 2019 novel coronavirus (COVID-19) infection have increased rapidly in Shanghai, China. Nevertheless, there is no widely used unified rehabilitation treatment available for discharged patients with post-infection sequelae such as dyspnea, depression, and fatigue. To promote the rehabilitation of discharged patients, our team formulated Kangyi Qiangshen Gong exercise prescription on the basis of traditional Chinese medicine rehabilitation exercises (TCMRE). We designed a randomized controlled trial to evaluate the efficacy of rehabilitation and advantages of KQG for discharged patients with post-COVID-19 syndrome. METHODS/DESIGN: This is a parallel-design, two-arm, analyst assessor-blinded, randomized controlled trial. In total, 60 discharged patients with COVID-19 sequelae, aged from 20 to 80 years will be recruited and randomly assigned to the World Health Organization instructed breathing techniques (BT) group and the Kangyi Qiangshen Gong exercise prescription (KQG) group at a ratio of 1:1. The patients in the BT group will perform breathing techniques exercise, and the patients in the KQG group will perform KQG exercise. Both groups will perform exercises twice a day for 3 months. The primary outcome will be measured with the Modified Medical Research Council Dyspnea Scale, and the secondary outcomes will include the Modified Borg Scale, Fatigue Scale-14, Patient Health Questionnaire-9 Scale, Pittsburgh Sleep Quality Index, and the Respiratory Symptoms Scale. Clinical scales will be assessed at three points (pre-exercise, 3 months post-exercise, and 3 months follow-up). Adverse events will be recorded for safety assessment. DISCUSSION: This trial will serve high-quality evidence of the value of KQG for treating discharged patients with COVID-19 in rehabilitation period. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200059504. Registered on 03 May 2022. DISSEMINATION: The results will be published in peer-reviewed journals and disseminated through the study's website, and conferences.